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Neuromuscular Disorders FIGURE 31. High arches, hammertoes, and distal leg atrophy in a patient with inherited neuropathy. bulbar weakness may lead to rapid respiratory failure. On about intubation, which should be guided by the need for examination, diffuse areflexia is a key finding; there is not airway protection and measurement of forced vital capacity marked sensory loss, even in the setting of paresthesia. Miller- and negative inspiratory force, should be made before emer- Fisher variant of GBS presents with ataxia, ophthalmoplegia gence of hypoxemia. Both plasmapheresis and intravenous and antibodies to GQ1b ganglioside protein. immune globulin (IVIG) have equal efficacy in shortening The differential diagnosis of GBS includes botulism the time to recovery and the duration of ventilation. Serial (descending weakness), myasthenic crisis (without pain and treatment with IVIG after plasma exchange is not superior to paresthesia), acute myelopathies (hyperreflexia and upper either treatment alone and has not shown significant added motor neuron signs), West Nile virus infection (asymmetric benefit. Glucocorticoids are contraindicated in GBS and may paralysis, fever, and muscle pain), carcinomatous and sarcoid worsen outcome. Prognosis is favorable, with 80% of patients meningitis (slower course), Lyme disease, HIV seroconversion, resuming ambulation by 6 months after onset. Relapse porphyria, and tick paralysis. occurs in 6% of patients with GBS and requires repeated CSF analysis shows a pattern of a highly elevated protein treatment. level with a normal or mildly elevated leukocyte count (albu- KEY POINTS minocytologic dissociation) in 90% of patients. Early normal CSF does not rule out GBS. EMG is the confirmatory test and e Guillain-Barré syndrome is an acute autoimmune

level with a normal or mildly elevated leukocyte count (albu- KEY POINTS minocytologic dissociation) in 90% of patients. Early normal CSF does not rule out GBS. EMG is the confirmatory test and e Guillain-Barré syndrome is an acute autoimmune shows a predominantly demyelinating pattern; sensitivity is demyelinating polyradiculoneuropathy that presents initially low but 90% by week 5. Initiation of treatment should with rapidly progressive ascending flaccid weakness. not await EMG confirmation; a negative early study should be e All patients with Guillain-Barré syndrome should be repeated later if the diagnosis remains suspected. Additional hospitalized for close respiratory and cardiovascular studies, such as spinal MRI and serologic testing for Lyme dis- monitoring; plasmapheresis and intravenous immune ease, HIV, and myasthenia antibodies, may be considered in globulin have equal efficacy in shortening the time to appropriate clinical settings. recovery and the duration of ventilation. Therapy includes supportive management and immu- e Glucocorticoids are contraindicated in Guillain-Barré notherapy. All patients with GBS should be hospitalized for syndrome and may worsen outcome. close respiratory and cardiovascular monitoring. Decisions 82

Neuromuscular Disorders Chronic Inflammatory Demyelinating Paraproteinemic Neuropathy Polyradiculoneuropathy Paraproteinemic neuropathy frequently presents as a symmetric Chronic inflammatory demyelinating polyradiculoneuropathy distal sensory neuropathy, but sensorimotor, multifocal motor, (CIDP) is a potentially treatable autoimmune neuropathy. or cranial nerve variants also are possible. Therefore, all patients CIDP often presents with a progressive or relapsing symmetric with peripheral neuropathy should be screened for parapro- proximal and distal weakness and sensory symptoms with dif- teinemia. Neuropathies associated with monoclonal proteins fuse areflexia. Its temporal course is often subacute with pro- occur in monoclonal gammopathy of undetermined signifi- gression after 8 weeks of onset. Atypical forms include multi- cance, multiple myeloma, amyloidosis, and other hematologic focal asymmetric and distal symmetric variants, but respiratory malignancies. (See MKSAP 19 Oncology.) Diagnosis depends on failure is rare. CIDP may be isolated or occur in the setting of the detection of monoclonal proteins, and treatment is based on several other systemic conditions, including diabetes mellitus, the underlying condition. A CIDP-like severe polyneuropathy lymphoma, and HIV. CSF findings are like those of GBS, and a may occur in paraproteinemic neuropathy in association with demyelinating pattern on EMG is the key to diagnosis. Nerve organomegaly, endocrinopathy, monoclonal plasma cell dis- biopsy is often unnecessary but, in complex presentations, can order, and skin changes (POEMS syndrome); this syndrome differentiate CIDP from vasculitis or amyloidosis. First-line always is associated with A paraproteinemia. Treatment is treatments include glucocorticoids, periodic IVIG, or plasma similar to that of multiple myeloma and may reverse neuro- exchange, which all have similar efficacy. Treatment is typi- pathic symptoms. cally continued for at least 6 months. Half of patients achieve remission, but the other half relapse and require resumption Autonomic Neuropathy of immunotherapy. Second-line therapies, including azathio- Autonomic neuropathies manifest as diffuse or focal impair- prine, mycophenolate mofetil, cyclosporine, or cyclophospha- ment of cholinergic or sympathetic autonomic systems. mide, are often used off-label to treat refractory disease. Whereas diabetes, amyloidosis, and HIV are common disor- Subcutaneous immunoglobin therapy is available for preven- ders underlying secondary autonomic neuropathy, primary tion of relapse in CIDP. autoimmune ganglionopathy is an important and potentially

Chronic Inflammatory Demyelinating Paraproteinemic Neuropathy Polyradiculoneuropathy Paraproteinemic neuropathy frequently presents as a symmetric Chronic inflammatory demyelinating polyradiculoneuropathy distal sensory neuropathy, but sensorimotor, multifocal motor, (CIDP) is a potentially treatable autoimmune neuropathy. or cranial nerve variants also are possible. Therefore, all patients CIDP often presents with a progressive or relapsing symmetric with peripheral neuropathy should be screened for parapro- proximal and distal weakness and sensory symptoms with dif- teinemia. Neuropathies associated with monoclonal proteins fuse areflexia. Its temporal course is often subacute with pro- occur in monoclonal gammopathy of undetermined signifi- gression after 8 weeks of onset. Atypical forms include multi- cance, multiple myeloma, amyloidosis, and other hematologic focal asymmetric and distal symmetric variants, but respiratory malignancies. (See MKSAP 19 Oncology.) Diagnosis depends on failure is rare. CIDP may be isolated or occur in the setting of the detection of monoclonal proteins, and treatment is based on several other systemic conditions, including diabetes mellitus, the underlying condition. A CIDP-like severe polyneuropathy lymphoma, and HIV. CSF findings are like those of GBS, and a may occur in paraproteinemic neuropathy in association with demyelinating pattern on EMG is the key to diagnosis. Nerve organomegaly, endocrinopathy, monoclonal plasma cell dis- biopsy is often unnecessary but, in complex presentations, can order, and skin changes (POEMS syndrome); this syndrome differentiate CIDP from vasculitis or amyloidosis. First-line always is associated with A paraproteinemia. Treatment is treatments include glucocorticoids, periodic IVIG, or plasma similar to that of multiple myeloma and may reverse neuro- exchange, which all have similar efficacy. Treatment is typi- pathic symptoms. cally continued for at least 6 months. Half of patients achieve remission, but the other half relapse and require resumption Autonomic Neuropathy of immunotherapy. Second-line therapies, including azathio- Autonomic neuropathies manifest as diffuse or focal impair- prine, mycophenolate mofetil, cyclosporine, or cyclophospha- ment of cholinergic or sympathetic autonomic systems. mide, are often used off-label to treat refractory disease. Whereas diabetes, amyloidosis, and HIV are common disor- Subcutaneous immunoglobin therapy is available for preven- ders underlying secondary autonomic neuropathy, primary tion of relapse in CIDP. autoimmune ganglionopathy is an important and potentially treatable cause of autonomic neuropathy that is often associ- Critical IIIness Neuropathy ated with antibodies against ganglionic nicotinic acetylcholine Prolonged intensive care treatment, particularly in associa- receptors. The presentation may range from acute pandysau- tion with sepsis and multiorgan failure, can lead to diffuse tonomia to chronic focal autonomic dysfunction. Antibody weakness, an inability to wean patients from ventilators, testing and skin biopsy help with diagnosis. Response to IVIG, and prolonged posthospitalization weakness. Weakness may plasmapheresis, or immunosuppression is common. be secondary to critical illness myopathy, critical illness Amyloid neuropathy is caused by extracellular deposition axonal neuropathy, or a combination of the two. Critical ill- of amyloid protein in peripheral nerves and other tissues. ness myopathy is more common, less severe, and potentially Amyloidosis starts with painful small-fiber neuropathy and caused by channelopathy (a disease involving dysfunction of progressively causes major autonomic impairment and weak- a cellular ion channel) triggered by sepsis and systemic dis- ness and multiorgan involvement. Bilateral carpal tunnel syn- ease. Critical illness neuropathy, on the other hand, is asso- drome can be seen. ciated with microcirculatory axonal damage and a more Primary amyloidosis is associated with monoclonal pro- protracted recovery. EMG can differentiate between the two, teins, whereas familial amyloidosis is secondary to transthyre- but often components of both are simultaneously present. tin gene mutation (see MKSAP 19 Oncology). Patisiran, a Differential diagnosis includes GBS, myasthenia gravis, vas- small interfering ribonucleic acid, and inotersen, an antisense culitis, and central weakness. No definitive treatment is oligonucleotide, are FDA approved treatments hereditary available, but appropriate glycemic control, early mobiliza- transthyretin-related neuropathy. tion and therapy, and minimizing glucocorticoid use improve prognosis. Amyotrophic Lateral Sclerosis Amyotrophic lateral sclerosis (ALS) is a neurodegenerative ¢ Critical illness axonal polyneuropathy often coexists disease of motor neurons that causes progressive weakness, with critical illness myopathy and can lead to diffuse atrophy, and early death. This motor neuron disease often weakness, an inability to wean patients from ventila- begins as isolated extremity or bulbar weakness (dysphagia, tors, and prolonged posthospitalization weakness. dysarthria) but relentlessly spreads to other regions. Upper ¢ No definitive treatment is available for critical illness (hyperreflexia, spasticity, and extensor plantar response) and neuropathy, but appropriate glycemic control, early lower (atrophy and fasciculation) motor neuron signs and the mobilization and therapy, and minimizing glucocorti- absence of sensory deficits are characteristic. Frontotemporal coid use improve prognosis. dementia occurs in 20% of affected patients, but oculomotor palsy, incontinence, and tremor are atypical. Diagnosis is

treatable cause of autonomic neuropathy that is often associ- Critical IIIness Neuropathy ated with antibodies against ganglionic nicotinic acetylcholine Prolonged intensive care treatment, particularly in associa- receptors. The presentation may range from acute pandysau- tion with sepsis and multiorgan failure, can lead to diffuse tonomia to chronic focal autonomic dysfunction. Antibody weakness, an inability to wean patients from ventilators, testing and skin biopsy help with diagnosis. Response to IVIG, and prolonged posthospitalization weakness. Weakness may plasmapheresis, or immunosuppression is common. be secondary to critical illness myopathy, critical illness Amyloid neuropathy is caused by extracellular deposition axonal neuropathy, or a combination of the two. Critical ill- of amyloid protein in peripheral nerves and other tissues. ness myopathy is more common, less severe, and potentially Amyloidosis starts with painful small-fiber neuropathy and caused by channelopathy (a disease involving dysfunction of progressively causes major autonomic impairment and weak- a cellular ion channel) triggered by sepsis and systemic dis- ness and multiorgan involvement. Bilateral carpal tunnel syn- ease. Critical illness neuropathy, on the other hand, is asso- drome can be seen. ciated with microcirculatory axonal damage and a more Primary amyloidosis is associated with monoclonal pro- protracted recovery. EMG can differentiate between the two, teins, whereas familial amyloidosis is secondary to transthyre- but often components of both are simultaneously present. tin gene mutation (see MKSAP 19 Oncology). Patisiran, a Differential diagnosis includes GBS, myasthenia gravis, vas- small interfering ribonucleic acid, and inotersen, an antisense culitis, and central weakness. No definitive treatment is oligonucleotide, are FDA approved treatments hereditary available, but appropriate glycemic control, early mobiliza- transthyretin-related neuropathy. tion and therapy, and minimizing glucocorticoid use improve prognosis. Amyotrophic Lateral Sclerosis Amyotrophic lateral sclerosis (ALS) is a neurodegenerative ¢ Critical illness axonal polyneuropathy often coexists disease of motor neurons that causes progressive weakness, with critical illness myopathy and can lead to diffuse atrophy, and early death. This motor neuron disease often weakness, an inability to wean patients from ventila- begins as isolated extremity or bulbar weakness (dysphagia, tors, and prolonged posthospitalization weakness. dysarthria) but relentlessly spreads to other regions. Upper ¢ No definitive treatment is available for critical illness (hyperreflexia, spasticity, and extensor plantar response) and neuropathy, but appropriate glycemic control, early lower (atrophy and fasciculation) motor neuron signs and the mobilization and therapy, and minimizing glucocorti- absence of sensory deficits are characteristic. Frontotemporal coid use improve prognosis. dementia occurs in 20% of affected patients, but oculomotor palsy, incontinence, and tremor are atypical. Diagnosis is 83

Neuromuscular Disorders based on clinical evidence of both upper and lower motor Diagnosis of MG is based on clinical, serologic, and EMG neuron signs on examination and EMG evidence of lower findings. Disease-specific antibodies are found in 90% of motor neuron signs in at least two (probable ALS) or more patients; of these, 85% have typical MG with acetylcholine (definite ALS) regions. Alternative diagnoses also must be receptor antibodies, but 5% have anti-muscle-specific kinase excluded by brain and cervical spinal imaging and laboratory (MuSK) or anti-lipoprotein receptor-related protein 4 (LRP4) testing; cervical cord compression, vitamin B,, and copper antibodies. MuSK-positive myasthenia is more likely to cause deficiencies, Lyme disease, hyperparathyroidism, and thyro- focal or severe bulbar, cervical, or respiratory weakness. The toxicosis must be excluded. Multifocal motor neuropathy is a characteristic EMG finding of MG is a decremental response to treatable ALS mimic characterized by severe weakness with repetitive stimulation. All patients with MG should undergo minimal atrophy, absence of upper motor neuron signs, and chest CT to screen for thymoma, a tumor associated with the EMG evidence of motor conduction block. disease. Treatment of ALS is supportive and should involve multi- Symptomatic treatment of ocular and mild generalized disciplinary care. Riluzole, a glutamate release blocker, and myasthenia usually starts with the cholinesterase inhibitor edavarone, a free radical scavenger, are FDA-approved treat- pyridostigmine. In those with more advanced disease, immu- ments for ALS, but they offer only modest benefits in term of nosuppressive therapy is required. Oral glucocorticoids often survival and functional decline. Noninvasive ventilation, are used as first-line treatment but can cause transient exacer- nutritional support (including percutaneous endoscopic gas- bation at high doses and should be titrated upward slowly in trostomy), and treatment of pseudobulbar affect by dex- patients with mild to moderate weakness. In the presence of tromethorphan-quinidine also have shown some benefit. prominent bulbar or generalized weakness and in myasthenic Prognosis and goals of care should be discussed with the crisis, treatment with IVIG or plasmapheresis should precede patient early in the disease course to avoid unwanted diagnos- initiation of glucocorticoids because of the risk of triggering tic and therapeutic measures. respiratory failure. The immunosuppressants azathioprine, mycophenolate mofetil, cyclosporine, and eculizumab are effective long-term maintenance therapies. However, these ¢ Amyotrophic lateral sclerosis (ALS) is a neurodegenera- drugs have a delayed onset of action, and bridging therapy tive disease of motor neurons that causes progressive with concomitant glucocorticoids, IVIG, or plasmapheresis is weakness, atrophy, and early death; 20% of patients usually required. with ALS will develop frontotemporal dementia. Thymectomy should be performed in all patients with e Riluzole and edavarone are FDA-approved treatments thymoma and offered as an option to (potentially) avoid or for ALS, but they offer only modest benefits in term of minimize immunotherapy in other patients with active disease survival and functional decline. who are younger than 65 years and within 3 years of diagnosis. MuSK-positive myasthenia responds well to plasmapher- esis and glucocorticoids but requires aggressive maintenance immunosuppression. Prolonged remission has been reported Neuromuscular Junction Disorders with rituximab (off-label use); thymectomy and pyridostig- Myasthenia Gravis mine are not helpful. Myasthenia gravis (MG) is an autoimmune disease of the postsynaptic neuromuscular junction associated with anti- bodies to acetylcholine receptors. Onset most commonly ¢ Onset of myasthenia gravis (MG) most commonly occurs in the third decade of life in women and after age occurs in the third decade of life in women and after

based on clinical evidence of both upper and lower motor Diagnosis of MG is based on clinical, serologic, and EMG neuron signs on examination and EMG evidence of lower findings. Disease-specific antibodies are found in 90% of motor neuron signs in at least two (probable ALS) or more patients; of these, 85% have typical MG with acetylcholine (definite ALS) regions. Alternative diagnoses also must be receptor antibodies, but 5% have anti-muscle-specific kinase excluded by brain and cervical spinal imaging and laboratory (MuSK) or anti-lipoprotein receptor-related protein 4 (LRP4) testing; cervical cord compression, vitamin B,, and copper antibodies. MuSK-positive myasthenia is more likely to cause deficiencies, Lyme disease, hyperparathyroidism, and thyro- focal or severe bulbar, cervical, or respiratory weakness. The toxicosis must be excluded. Multifocal motor neuropathy is a characteristic EMG finding of MG is a decremental response to treatable ALS mimic characterized by severe weakness with repetitive stimulation. All patients with MG should undergo minimal atrophy, absence of upper motor neuron signs, and chest CT to screen for thymoma, a tumor associated with the EMG evidence of motor conduction block. disease. Treatment of ALS is supportive and should involve multi- Symptomatic treatment of ocular and mild generalized disciplinary care. Riluzole, a glutamate release blocker, and myasthenia usually starts with the cholinesterase inhibitor edavarone, a free radical scavenger, are FDA-approved treat- pyridostigmine. In those with more advanced disease, immu- ments for ALS, but they offer only modest benefits in term of nosuppressive therapy is required. Oral glucocorticoids often survival and functional decline. Noninvasive ventilation, are used as first-line treatment but can cause transient exacer- nutritional support (including percutaneous endoscopic gas- bation at high doses and should be titrated upward slowly in trostomy), and treatment of pseudobulbar affect by dex- patients with mild to moderate weakness. In the presence of tromethorphan-quinidine also have shown some benefit. prominent bulbar or generalized weakness and in myasthenic Prognosis and goals of care should be discussed with the crisis, treatment with IVIG or plasmapheresis should precede patient early in the disease course to avoid unwanted diagnos- initiation of glucocorticoids because of the risk of triggering tic and therapeutic measures. respiratory failure. The immunosuppressants azathioprine, mycophenolate mofetil, cyclosporine, and eculizumab are effective long-term maintenance therapies. However, these ¢ Amyotrophic lateral sclerosis (ALS) is a neurodegenera- drugs have a delayed onset of action, and bridging therapy tive disease of motor neurons that causes progressive with concomitant glucocorticoids, IVIG, or plasmapheresis is weakness, atrophy, and early death; 20% of patients usually required. with ALS will develop frontotemporal dementia. Thymectomy should be performed in all patients with e Riluzole and edavarone are FDA-approved treatments thymoma and offered as an option to (potentially) avoid or for ALS, but they offer only modest benefits in term of minimize immunotherapy in other patients with active disease survival and functional decline. who are younger than 65 years and within 3 years of diagnosis. MuSK-positive myasthenia responds well to plasmapher- esis and glucocorticoids but requires aggressive maintenance immunosuppression. Prolonged remission has been reported Neuromuscular Junction Disorders with rituximab (off-label use); thymectomy and pyridostig- Myasthenia Gravis mine are not helpful. Myasthenia gravis (MG) is an autoimmune disease of the postsynaptic neuromuscular junction associated with anti- bodies to acetylcholine receptors. Onset most commonly ¢ Onset of myasthenia gravis (MG) most commonly occurs in the third decade of life in women and after age occurs in the third decade of life in women and after 50 years in men. Ptosis and diplopia are the first manifesta- age 50 years in men, with ptosis, diplopia, and fluctuat-

based on clinical evidence of both upper and lower motor Diagnosis of MG is based on clinical, serologic, and EMG neuron signs on examination and EMG evidence of lower findings. Disease-specific antibodies are found in 90% of motor neuron signs in at least two (probable ALS) or more patients; of these, 85% have typical MG with acetylcholine (definite ALS) regions. Alternative diagnoses also must be receptor antibodies, but 5% have anti-muscle-specific kinase excluded by brain and cervical spinal imaging and laboratory (MuSK) or anti-lipoprotein receptor-related protein 4 (LRP4) testing; cervical cord compression, vitamin B,, and copper antibodies. MuSK-positive myasthenia is more likely to cause deficiencies, Lyme disease, hyperparathyroidism, and thyro- focal or severe bulbar, cervical, or respiratory weakness. The toxicosis must be excluded. Multifocal motor neuropathy is a characteristic EMG finding of MG is a decremental response to treatable ALS mimic characterized by severe weakness with repetitive stimulation. All patients with MG should undergo minimal atrophy, absence of upper motor neuron signs, and chest CT to screen for thymoma, a tumor associated with the EMG evidence of motor conduction block. disease. Treatment of ALS is supportive and should involve multi- Symptomatic treatment of ocular and mild generalized disciplinary care. Riluzole, a glutamate release blocker, and myasthenia usually starts with the cholinesterase inhibitor edavarone, a free radical scavenger, are FDA-approved treat- pyridostigmine. In those with more advanced disease, immu- ments for ALS, but they offer only modest benefits in term of nosuppressive therapy is required. Oral glucocorticoids often survival and functional decline. Noninvasive ventilation, are used as first-line treatment but can cause transient exacer- nutritional support (including percutaneous endoscopic gas- bation at high doses and should be titrated upward slowly in trostomy), and treatment of pseudobulbar affect by dex- patients with mild to moderate weakness. In the presence of tromethorphan-quinidine also have shown some benefit. prominent bulbar or generalized weakness and in myasthenic Prognosis and goals of care should be discussed with the crisis, treatment with IVIG or plasmapheresis should precede patient early in the disease course to avoid unwanted diagnos- initiation of glucocorticoids because of the risk of triggering tic and therapeutic measures. respiratory failure. The immunosuppressants azathioprine, mycophenolate mofetil, cyclosporine, and eculizumab are effective long-term maintenance therapies. However, these ¢ Amyotrophic lateral sclerosis (ALS) is a neurodegenera- drugs have a delayed onset of action, and bridging therapy tive disease of motor neurons that causes progressive with concomitant glucocorticoids, IVIG, or plasmapheresis is weakness, atrophy, and early death; 20% of patients usually required. with ALS will develop frontotemporal dementia. Thymectomy should be performed in all patients with e Riluzole and edavarone are FDA-approved treatments thymoma and offered as an option to (potentially) avoid or for ALS, but they offer only modest benefits in term of minimize immunotherapy in other patients with active disease survival and functional decline. who are younger than 65 years and within 3 years of diagnosis. MuSK-positive myasthenia responds well to plasmapher- esis and glucocorticoids but requires aggressive maintenance immunosuppression. Prolonged remission has been reported Neuromuscular Junction Disorders with rituximab (off-label use); thymectomy and pyridostig- Myasthenia Gravis mine are not helpful. Myasthenia gravis (MG) is an autoimmune disease of the postsynaptic neuromuscular junction associated with anti- bodies to acetylcholine receptors. Onset most commonly ¢ Onset of myasthenia gravis (MG) most commonly occurs in the third decade of life in women and after age occurs in the third decade of life in women and after 50 years in men. Ptosis and diplopia are the first manifesta- age 50 years in men, with ptosis, diplopia, and fluctuat- tions in two thirds of patients, although only half of these ing painless weakness without sensory loss being typi-

based on clinical evidence of both upper and lower motor Diagnosis of MG is based on clinical, serologic, and EMG neuron signs on examination and EMG evidence of lower findings. Disease-specific antibodies are found in 90% of motor neuron signs in at least two (probable ALS) or more patients; of these, 85% have typical MG with acetylcholine (definite ALS) regions. Alternative diagnoses also must be receptor antibodies, but 5% have anti-muscle-specific kinase excluded by brain and cervical spinal imaging and laboratory (MuSK) or anti-lipoprotein receptor-related protein 4 (LRP4) testing; cervical cord compression, vitamin B,, and copper antibodies. MuSK-positive myasthenia is more likely to cause deficiencies, Lyme disease, hyperparathyroidism, and thyro- focal or severe bulbar, cervical, or respiratory weakness. The toxicosis must be excluded. Multifocal motor neuropathy is a characteristic EMG finding of MG is a decremental response to treatable ALS mimic characterized by severe weakness with repetitive stimulation. All patients with MG should undergo minimal atrophy, absence of upper motor neuron signs, and chest CT to screen for thymoma, a tumor associated with the EMG evidence of motor conduction block. disease. Treatment of ALS is supportive and should involve multi- Symptomatic treatment of ocular and mild generalized disciplinary care. Riluzole, a glutamate release blocker, and myasthenia usually starts with the cholinesterase inhibitor edavarone, a free radical scavenger, are FDA-approved treat- pyridostigmine. In those with more advanced disease, immu- ments for ALS, but they offer only modest benefits in term of nosuppressive therapy is required. Oral glucocorticoids often survival and functional decline. Noninvasive ventilation, are used as first-line treatment but can cause transient exacer- nutritional support (including percutaneous endoscopic gas- bation at high doses and should be titrated upward slowly in trostomy), and treatment of pseudobulbar affect by dex- patients with mild to moderate weakness. In the presence of tromethorphan-quinidine also have shown some benefit. prominent bulbar or generalized weakness and in myasthenic Prognosis and goals of care should be discussed with the crisis, treatment with IVIG or plasmapheresis should precede patient early in the disease course to avoid unwanted diagnos- initiation of glucocorticoids because of the risk of triggering tic and therapeutic measures. respiratory failure. The immunosuppressants azathioprine, mycophenolate mofetil, cyclosporine, and eculizumab are effective long-term maintenance therapies. However, these ¢ Amyotrophic lateral sclerosis (ALS) is a neurodegenera- drugs have a delayed onset of action, and bridging therapy tive disease of motor neurons that causes progressive with concomitant glucocorticoids, IVIG, or plasmapheresis is weakness, atrophy, and early death; 20% of patients usually required. with ALS will develop frontotemporal dementia. Thymectomy should be performed in all patients with e Riluzole and edavarone are FDA-approved treatments thymoma and offered as an option to (potentially) avoid or for ALS, but they offer only modest benefits in term of minimize immunotherapy in other patients with active disease survival and functional decline. who are younger than 65 years and within 3 years of diagnosis. MuSK-positive myasthenia responds well to plasmapher- esis and glucocorticoids but requires aggressive maintenance immunosuppression. Prolonged remission has been reported Neuromuscular Junction Disorders with rituximab (off-label use); thymectomy and pyridostig- Myasthenia Gravis mine are not helpful. Myasthenia gravis (MG) is an autoimmune disease of the postsynaptic neuromuscular junction associated with anti- bodies to acetylcholine receptors. Onset most commonly ¢ Onset of myasthenia gravis (MG) most commonly occurs in the third decade of life in women and after age occurs in the third decade of life in women and after 50 years in men. Ptosis and diplopia are the first manifesta- age 50 years in men, with ptosis, diplopia, and fluctuat- tions in two thirds of patients, although only half of these ing painless weakness without sensory loss being typi- patients develop generalized myasthenia, typically within cal symptoms; all patients with MG should undergo

50 years in men. Ptosis and diplopia are the first manifesta- age 50 years in men, with ptosis, diplopia, and fluctuat- tions in two thirds of patients, although only half of these ing painless weakness without sensory loss being typi- patients develop generalized myasthenia, typically within cal symptoms; all patients with MG should undergo 2 years. Early bulbar and cervical involvement is seen in 10% chest CT to screen for thymoma, a tumor associated of patients. Fluctuating painless weakness without sensory with the disease. loss is typical. Weakness may be missed on clinical examina- e¢ Symptomatic treatment of ocular and mild generalized tion unless fatigability is assessed by sustained or repeated myasthenia gravis usually starts with the cholinesterase activation of muscles. The presence of respiratory symptoms inhibitor pyridostigmine; in those with more advanced should prompt close monitoring of respiratory parameters disease, immunosuppressive therapy is required, as is because of the risk of rapid respiratory failure (myasthenic thymectomy for those with thymoma. crisis). This crisis can occur as part of the natural history of bulbar or generalized myasthenia or be triggered by external factors, including infection, surgery, or certain medications Lambert-Eaton Myasthenic Syndrome (especially aminoglycosides, quinolones, magnesium, B-blockers, Lambert-Eaton myasthenic syndrome is an autoimmune and hydroxychloroquine). disorder of the presynaptic neuromuscular junction 84

Neuromuscular Disorders associated with antibodies against the voltage-gated cal- Myopathies cium channel. This disorder presents similarly to MG, Overview except that weakness improves with exercise, and hypore- Classification of myopathies is based on clinical and patho- flexia and dysautonomia are present. Diagnosis is con- firmed by detection of serum anti-voltage-gated calcium logic characteristics and acquired versus inherited causes channel antibodies (90%) and the EMG finding of aug- (Table 49). Most myopathies involve symmetric weakness of mented motor response to rapid repetitive stimulation. the proximal limb muscles. A normal sensory and reflex Malignancy, especially small cell lung cancer, is found in examination can differentiate myopathy from neuropathy. half of patients. Treatment consists of treating any underly- Additional features that can indicate a specific diagnosis ing malignancy or, in nonparaneoplastic disease, immuno- include the clinical course; the presence of pain and stiffness; suppression, IVIG, or plasmapheresis. Amifampridine can atypical distribution in ocular, bulbar, or distal limb muscles; provide symptomatic benefit. and episodic symptoms (Table 50). TABLE 49. Classification of Myopathies | Class Examples Features | Inherited myopathies | Muscular dystrophies Duchenne Early onset, fulminant

TABLE 49. Classification of Myopathies | Class Examples Features | Inherited myopathies | Muscular dystrophies Duchenne Early onset, fulminant | Becker, Emery-Dreifuss Early onset, survival to adulthood, cardiac disease Limb-girdle, facioscapulohumeral, Variable onset, slow course oculopharyngeal Myotonic dystrophy Type 1 Myotonia, distal weakness, ptosis with lower facial weakness, variable cognitive impairment, cataract, arrhythmia with cardiomyopathy, diabetes mellitus, thyroid disease Type 2 Myotonia, proximal weakness, milder course, systemic features similar to those of type 1 | Congenital myopathies Nemaline myopathy, centronuclear myopathy, Childhood onset, focal weakness in distal forms, central core myopathy, distal myopathies predisposition to exercise-induced cramping and malignant hyperthermia in central core myopathy

| Congenital myopathies Nemaline myopathy, centronuclear myopathy, Childhood onset, focal weakness in distal forms, central core myopathy, distal myopathies predisposition to exercise-induced cramping and malignant hyperthermia in central core myopathy Metabolic myopathies Acid maltase deficiency (Pompe disease), CPT II Exercise intolerance, myoglobinuria, myalgia, deficiency, McArdle disease (myophosphorylase progressive proximal and respiratory weakness in deficiency), other lipid and glycogen storage acid maltase deficiency disorders Mitochondrial myopathies MERRF, MELAS, MNGIE, Kearns-Sayre syndrome Childhood or early adulthood onset, fluctuating course, wide spectrum with variable systemic comorbidity, ophthalmoplegia, bulbar symptoms, elevated plasma lactic acid level Acquired myopathies Inflammatory Dermatomyositis, polymyositis, immune-mediated Highly elevated creatine kinase level, subacute necrotizing myopathy course, association with malignancy, dermatologic signs in dermatomyositis

Inflammatory Dermatomyositis, polymyositis, immune-mediated Highly elevated creatine kinase level, subacute necrotizing myopathy course, association with malignancy, dermatologic signs in dermatomyositis Inclusion body myositis Onset usually after age 50 years, asymmetric progressive weakness with atrophy, distal arm and quadriceps involvement Endocrine-related Hypothyroidism, hyperthyroidism, hyperparathyroidism, Addison disease, Cushing syndrome, acromegaly, vitamin D deficiency, hypokalemia Systemic disease Systemic lupus erythematosus, mixed connective tissue disease, systemic sclerosis, critical illness, paraneoplastic Toxic and drug-related Ethanol, statins, gemfibrozil, fenofibrate, ezetimibe, Statin myopathy as possible cause of mildly to glucocorticoids, anti-HIV and antimalarial agents, highly elevated creatine kinase level interferons, amphotericin B, amiodarone, | immunophilins, immune checkpoint inhibitors

Toxic and drug-related Ethanol, statins, gemfibrozil, fenofibrate, ezetimibe, Statin myopathy as possible cause of mildly to glucocorticoids, anti-HIV and antimalarial agents, highly elevated creatine kinase level interferons, amphotericin B, amiodarone, | immunophilins, immune checkpoint inhibitors CPT Il deficiency = carnitine palmitoyltransferase II deficiency; MELAS = mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes syndrome; MERRF = myoclonic | epilepsy with ragged red fibers; MNGIE = mitochondrial neurogastrointestinal encephalopathy. l = a 85

Neuromuscular Disorders TABLE 50. Clinical Features of Myopathies Inclusion body myositis has a slowly progressive course and causes early weakness and atrophy of distal upper extremity Clinical Features Differential Diagnosis flexors, quadriceps, and bulbar muscles. Muscle biopsy reveals Pain Metabolic, toxic, infectious, inflammatory, inflammation and characteristic inclusion bodies. See MKSAP and mitochondrial myopathies 19 Rheumatology for further information on inflammatory Stiffness Myotonic dystrophy, myotonic myopathy. channelopathies, hyperkalemic periodic paralysis, hypothyroidism; differential diagnosis: stiff person syndrome Endocrine-Related Myopathy Rapid course Inflammatory, toxic, autoimmune, and Hypothyroid myopathy can cause diffuse myalgia, proximal endocrine myopathies weakness, and myoedema (muscle mounding after percus- | } Very slow course, Muscular dystrophies, congenital plus or minus myopathies, metabolic myopathies sion). Hyperthyroidism also can cause myopathy in associa- focal atrophy tion with fasciculation, ophthalmoplegia and hyperreflexia.

Very slow course, Muscular dystrophies, congenital plus or minus myopathies, metabolic myopathies sion). Hyperthyroidism also can cause myopathy in associa- focal atrophy tion with fasciculation, ophthalmoplegia and hyperreflexia. Fluctuating Mitochondrial myopathy, myasthenia An excess of endogenous or exogenous glucocorticosteroids, weakness gravis parathyroid or pituitary dysfunction, and vitamin D deficiency

Very slow course, Muscular dystrophies, congenital plus or minus myopathies, metabolic myopathies sion). Hyperthyroidism also can cause myopathy in associa- focal atrophy tion with fasciculation, ophthalmoplegia and hyperreflexia. Fluctuating Mitochondrial myopathy, myasthenia An excess of endogenous or exogenous glucocorticosteroids, weakness gravis parathyroid or pituitary dysfunction, and vitamin D deficiency Myoglobinuria Toxic and infectious myopathy, trauma, | are other endocrine causes of myopathy. metabolic myopathies (CPT Il deficiency, McArdle disease, central core myopathy) | Toxic Myopathy Respiratory Muscular dystrophies, inflammatory, Toxic myopathy can be triggered by statins and other drugs muscle mitochondrial, and metabolic myopathies involvement (acid maltase deficiency, debrancher (see Table 49). Statins can cause a spectrum of symptoms, deficiency) ranging from mild myalgia to myopathy to rare cases of rhab- Cardiomyopathy = Myotonic dystrophies, muscular domyolysis. The risk of myopathy increases with higher dos- dystrophies (Emery-Dreifuss, Becker), | ages, the addition of fenofibrate or gemfibrozil, the addition mitochondrial and toxic myopathy of cytochrome P450 3A4 isozyme inhibitors, and the use of Cataract Myotonic dystrophies, mitochondrial lipophilic statins (simvastatin, atorvastatin, and lovastatin). myopathy Discontinuation of these agents should be considered if CPT II deficiency = carnitine palmitoyltransferase I! deficiency. | serum CK level is elevated (typically, >5-10 times the upper limit of normal) or in patients with weakness or severe pain. .

Myoglobinuria Toxic and infectious myopathy, trauma, | are other endocrine causes of myopathy. metabolic myopathies (CPT Il deficiency, McArdle disease, central core myopathy) | Toxic Myopathy Respiratory Muscular dystrophies, inflammatory, Toxic myopathy can be triggered by statins and other drugs muscle mitochondrial, and metabolic myopathies involvement (acid maltase deficiency, debrancher (see Table 49). Statins can cause a spectrum of symptoms, deficiency) ranging from mild myalgia to myopathy to rare cases of rhab- Cardiomyopathy = Myotonic dystrophies, muscular domyolysis. The risk of myopathy increases with higher dos- dystrophies (Emery-Dreifuss, Becker), | ages, the addition of fenofibrate or gemfibrozil, the addition mitochondrial and toxic myopathy of cytochrome P450 3A4 isozyme inhibitors, and the use of Cataract Myotonic dystrophies, mitochondrial lipophilic statins (simvastatin, atorvastatin, and lovastatin). myopathy Discontinuation of these agents should be considered if CPT II deficiency = carnitine palmitoyltransferase I! deficiency. | serum CK level is elevated (typically, >5-10 times the upper limit of normal) or in patients with weakness or severe pain. . Diagnosis is based on systematic clinical assessment, In patients deemed to significantly benefit from statins,

Myoglobinuria Toxic and infectious myopathy, trauma, | are other endocrine causes of myopathy. metabolic myopathies (CPT Il deficiency, McArdle disease, central core myopathy) | Toxic Myopathy Respiratory Muscular dystrophies, inflammatory, Toxic myopathy can be triggered by statins and other drugs muscle mitochondrial, and metabolic myopathies involvement (acid maltase deficiency, debrancher (see Table 49). Statins can cause a spectrum of symptoms, deficiency) ranging from mild myalgia to myopathy to rare cases of rhab- Cardiomyopathy = Myotonic dystrophies, muscular domyolysis. The risk of myopathy increases with higher dos- dystrophies (Emery-Dreifuss, Becker), | ages, the addition of fenofibrate or gemfibrozil, the addition mitochondrial and toxic myopathy of cytochrome P450 3A4 isozyme inhibitors, and the use of Cataract Myotonic dystrophies, mitochondrial lipophilic statins (simvastatin, atorvastatin, and lovastatin). myopathy Discontinuation of these agents should be considered if CPT II deficiency = carnitine palmitoyltransferase I! deficiency. | serum CK level is elevated (typically, >5-10 times the upper limit of normal) or in patients with weakness or severe pain. . Diagnosis is based on systematic clinical assessment, In patients deemed to significantly benefit from statins, muscle-related serum markers (creatine kinase [CK], aldo- retrial with a different statin should be considered after reso-

Myoglobinuria Toxic and infectious myopathy, trauma, | are other endocrine causes of myopathy. metabolic myopathies (CPT Il deficiency, McArdle disease, central core myopathy) | Toxic Myopathy Respiratory Muscular dystrophies, inflammatory, Toxic myopathy can be triggered by statins and other drugs muscle mitochondrial, and metabolic myopathies involvement (acid maltase deficiency, debrancher (see Table 49). Statins can cause a spectrum of symptoms, deficiency) ranging from mild myalgia to myopathy to rare cases of rhab- Cardiomyopathy = Myotonic dystrophies, muscular domyolysis. The risk of myopathy increases with higher dos- dystrophies (Emery-Dreifuss, Becker), | ages, the addition of fenofibrate or gemfibrozil, the addition mitochondrial and toxic myopathy of cytochrome P450 3A4 isozyme inhibitors, and the use of Cataract Myotonic dystrophies, mitochondrial lipophilic statins (simvastatin, atorvastatin, and lovastatin). myopathy Discontinuation of these agents should be considered if CPT II deficiency = carnitine palmitoyltransferase I! deficiency. | serum CK level is elevated (typically, >5-10 times the upper limit of normal) or in patients with weakness or severe pain. . Diagnosis is based on systematic clinical assessment, In patients deemed to significantly benefit from statins, muscle-related serum markers (creatine kinase [CK], aldo- retrial with a different statin should be considered after reso- lase), EMG findings, muscle biopsy, and, in certain cases, lution of muscle symptoms, with continued monitoring of

Diagnosis is based on systematic clinical assessment, In patients deemed to significantly benefit from statins, muscle-related serum markers (creatine kinase [CK], aldo- retrial with a different statin should be considered after reso- lase), EMG findings, muscle biopsy, and, in certain cases, lution of muscle symptoms, with continued monitoring of genetic testing. The serum CK level is elevated in many forms the CK level. A small subset of patients develops a necrotizing of myopathy and can be followed to monitor disease activity myositis that continues to progress after discontinuation of and response to treatment in inflammatory myopathies. Mild statins. These patients have a serum antibody to hydroxy- elevation of the serum CK level (<5 times normal) is not spe- methylglutaryl-coenzyme A receptor and may respond to cific to myopathies and also can be seen in ALS, CIDP, muscle immunosuppression.

and response to treatment in inflammatory myopathies. Mild statins. These patients have a serum antibody to hydroxy- elevation of the serum CK level (<5 times normal) is not spe- methylglutaryl-coenzyme A receptor and may respond to cific to myopathies and also can be seen in ALS, CIDP, muscle immunosuppression. trauma, and persistent elevation of the serum CK level without weakness (benign hyperCKemia). EMG can confirm the pres- Inherited Myopathies ence of changes associated with myopathy (low amplitude, Inherited myopathies are listed in Table 49. Many of these dis- short duration, polyphasic shape of motor unit potentials). orders develop early in life, but some present in adulthood. Muscle biopsy is the most helpful test to confirm the diagnosis Myotonic dystrophies are systemic diseases associated with of myopathy, but in some hereditary myopathies, genetic test- myotonia, an impairment of muscle relaxation causing stiff- ing can provide the confirmation without need for biopsy. ness and a delayed hand-grip release. Myotonic dystrophy type 1 causes distal weakness and is associated with cataracts, fron- tal balding, cardiac and endocrine disease, and mild cognitive e Diagnosis of a myopathy is based on systematic clinical impairment. Progression of weakness is slow, but diagnosis assessment, muscle-related serum markers, electromy- should prompt close monitoring for cardiac and pulmonary ographic findings, muscle biopsy, and (sometimes) disease that can cause premature mortality. genetic testing. Mitochondrial myopathy presents with significant varia- bility and can cause fatigue, myalgia, ophthalmoplegia, and Inflammatory Myopathy various extramuscular manifestations. Mitochondrial myopa- Polymyositis, dermatomyositis, immune-mediated necrotiz- thies should be suspected in the presence of a fluctuating ing myopathy, and inclusion body myositis are idiopathic course, multiorgan involvement, and maternal transmission. inflammatory myopathies. Polymyositis and dermatomyositis Adult-onset metabolic myopathies may present with iso- present with acute or subacute proximal muscle weakness. lated exercise-induced weakness, cramps, and myoglobinuria

trauma, and persistent elevation of the serum CK level without weakness (benign hyperCKemia). EMG can confirm the pres- Inherited Myopathies ence of changes associated with myopathy (low amplitude, Inherited myopathies are listed in Table 49. Many of these dis- short duration, polyphasic shape of motor unit potentials). orders develop early in life, but some present in adulthood. Muscle biopsy is the most helpful test to confirm the diagnosis Myotonic dystrophies are systemic diseases associated with of myopathy, but in some hereditary myopathies, genetic test- myotonia, an impairment of muscle relaxation causing stiff- ing can provide the confirmation without need for biopsy. ness and a delayed hand-grip release. Myotonic dystrophy type 1 causes distal weakness and is associated with cataracts, fron- tal balding, cardiac and endocrine disease, and mild cognitive e Diagnosis of a myopathy is based on systematic clinical impairment. Progression of weakness is slow, but diagnosis assessment, muscle-related serum markers, electromy- should prompt close monitoring for cardiac and pulmonary ographic findings, muscle biopsy, and (sometimes) disease that can cause premature mortality. genetic testing. Mitochondrial myopathy presents with significant varia- bility and can cause fatigue, myalgia, ophthalmoplegia, and Inflammatory Myopathy various extramuscular manifestations. Mitochondrial myopa- Polymyositis, dermatomyositis, immune-mediated necrotiz- thies should be suspected in the presence of a fluctuating ing myopathy, and inclusion body myositis are idiopathic course, multiorgan involvement, and maternal transmission. inflammatory myopathies. Polymyositis and dermatomyositis Adult-onset metabolic myopathies may present with iso- present with acute or subacute proximal muscle weakness. lated exercise-induced weakness, cramps, and myoglobinuria 86

Neuro-oncology and include many deficiencies of key metabolic pathways, posterior fossa. Brain MRI is preferred; contrast administration such as glycogen storage and fatty acid oxidation; the most improves diagnostic sensitivity. Management is determined by common types are carnitine palmitoyltransferase II deficiency tumor location and pathology. and McArdle disease. Acid maltase deficiency (Pompe disease) has an adult- e Head CT without contrast may be useful emergently to onset form associated with proximal and respiratory muscle assess for hemorrhage or herniation, but brain MRI is weakness. Diagnosis is based on assessment of o.-glucosidase preferred for the evaluation of intracranial tumors. activity and genetic testing. Alglucosidase alfa is FDA approved to prevent progression of weakness. Metastatic Brain Tumors Neuro-oncology Brain metastases are the most common intracranial tumors. The most likely sources are lung, breast, and kidney cancers

and include many deficiencies of key metabolic pathways, posterior fossa. Brain MRI is preferred; contrast administration such as glycogen storage and fatty acid oxidation; the most improves diagnostic sensitivity. Management is determined by common types are carnitine palmitoyltransferase II deficiency tumor location and pathology. and McArdle disease. Acid maltase deficiency (Pompe disease) has an adult- e Head CT without contrast may be useful emergently to onset form associated with proximal and respiratory muscle assess for hemorrhage or herniation, but brain MRI is weakness. Diagnosis is based on assessment of o.-glucosidase preferred for the evaluation of intracranial tumors. activity and genetic testing. Alglucosidase alfa is FDA approved to prevent progression of weakness. Metastatic Brain Tumors Neuro-oncology Brain metastases are the most common intracranial tumors. The most likely sources are lung, breast, and kidney cancers Approach to Intracranial Tumors and melanoma. Metastases can be solitary but are more often multiple. These metastases typically appear as ring-enhancing Both benign and malignant intracranial tumors can have dev- lesions on postcontrast MRIs, usually at the gray-white corti- astating neurologic consequences because of the space con- cal junction. Survival is generally measured in weeks to straints within the skull and potential surgical inaccessibility. months. Most brain metastases are treated with whole-brain Presenting symptoms of intracranial tumors appear in Table 51. or more targeted radiation (stereotactic radiosurgery). Intracranial tumors usually present with a slow, progressive Resection may increase survival in younger patients with course of symptoms. Acute symptoms typically occur when good baseline function and a single or limited number of tumors cause seizure or hemorrhage. metastases; it may also be considered when the underlying Headache is a common symptom, although the classic diagnosis is uncertain. early morning headache is uncommon. Elevated intracra- Carcinomatous meningitis is a rare diagnosis that requires nial pressure (ICP) can cause the headache to increase with a high index of suspicion; presenting symptoms are variable coughing, sneezing, straining, or the Valsalva maneuver. and include head or neck pain, neurologic deficits, and altered Elevated ICP also is associated with nausea, vomiting, mental status. MRI typically shows dural thickening with blurry vision, papilledema, and an inability to abduct the nodular enhancement. Patients with leukemia or lymphoma eyes (bilateral abducens nerve [cranial nerve VI] palsy). whose initial symptoms are cranial nerve deficits or radicu- Elevated ICP also can lead to life-threatening herniation, lopathy may have evidence of nerve root enhancement on syncope, or cerebellar “fits” (episodic extension, flexion and postcontrast MRI of the brain and/or spine. Cerebrospinal fluid stiffening of limbs; loss of consciousness; slowed or irregu- (CSF) analysis with cytology and often flow cytometry is lar respiration; and pupil dilation), which may be confused required to make the diagnosis; because of limited sensitivity, with seizures. serial lumbar punctures are sometimes needed to establish the Head CT without contrast may be useful emergently to diagnosis. assess for hemorrhage or herniation but is not sensitive for detecting the presence of a mass lesion, especially in the

Approach to Intracranial Tumors and melanoma. Metastases can be solitary but are more often multiple. These metastases typically appear as ring-enhancing Both benign and malignant intracranial tumors can have dev- lesions on postcontrast MRIs, usually at the gray-white corti- astating neurologic consequences because of the space con- cal junction. Survival is generally measured in weeks to straints within the skull and potential surgical inaccessibility. months. Most brain metastases are treated with whole-brain Presenting symptoms of intracranial tumors appear in Table 51. or more targeted radiation (stereotactic radiosurgery). Intracranial tumors usually present with a slow, progressive Resection may increase survival in younger patients with course of symptoms. Acute symptoms typically occur when good baseline function and a single or limited number of tumors cause seizure or hemorrhage. metastases; it may also be considered when the underlying Headache is a common symptom, although the classic diagnosis is uncertain. early morning headache is uncommon. Elevated intracra- Carcinomatous meningitis is a rare diagnosis that requires nial pressure (ICP) can cause the headache to increase with a high index of suspicion; presenting symptoms are variable coughing, sneezing, straining, or the Valsalva maneuver. and include head or neck pain, neurologic deficits, and altered Elevated ICP also is associated with nausea, vomiting, mental status. MRI typically shows dural thickening with blurry vision, papilledema, and an inability to abduct the nodular enhancement. Patients with leukemia or lymphoma eyes (bilateral abducens nerve [cranial nerve VI] palsy). whose initial symptoms are cranial nerve deficits or radicu- Elevated ICP also can lead to life-threatening herniation, lopathy may have evidence of nerve root enhancement on syncope, or cerebellar “fits” (episodic extension, flexion and postcontrast MRI of the brain and/or spine. Cerebrospinal fluid stiffening of limbs; loss of consciousness; slowed or irregu- (CSF) analysis with cytology and often flow cytometry is lar respiration; and pupil dilation), which may be confused required to make the diagnosis; because of limited sensitivity, with seizures. serial lumbar punctures are sometimes needed to establish the Head CT without contrast may be useful emergently to diagnosis. assess for hemorrhage or herniation but is not sensitive for detecting the presence of a mass lesion, especially in the e Brain metastases are the most common intracranial TABLE 51. Presenting Symptoms/Findings of Central tumors that typically appear as ring-enhancing lesions Nervous System Tumors on postcontrast MRIs at the gray-white cortical junction. | Tumor Location Symptoms/Findings | ¢ Most brain metastases are treated with whole-brain or Brainstem Cranial nerve findings, elevated | more targeted radiation (stereotactic radiosurgery), but intracranial pressure? | | resection of a single or limited number of intracranial Cerebellum Ataxia, falls, imbalance, elevated metastases may increase survival in younger patients intracranial pressure? with good baseline function. | Frontal lobe Weakness, personality change, cognitive symptoms, or psychiatric symptoms

e Brain metastases are the most common intracranial TABLE 51. Presenting Symptoms/Findings of Central tumors that typically appear as ring-enhancing lesions Nervous System Tumors on postcontrast MRIs at the gray-white cortical junction. | Tumor Location Symptoms/Findings | ¢ Most brain metastases are treated with whole-brain or Brainstem Cranial nerve findings, elevated | more targeted radiation (stereotactic radiosurgery), but intracranial pressure? | | resection of a single or limited number of intracranial Cerebellum Ataxia, falls, imbalance, elevated metastases may increase survival in younger patients intracranial pressure? with good baseline function. | Frontal lobe Weakness, personality change, cognitive symptoms, or psychiatric symptoms Occipital lobe Homonymous hemianopia Parietal lobe Primary Central Nervous Numbness, paresthesia | Temporal lobe Amnesia System Tumors Dominant Aphasia Meningiomas hemisphere Meningioma is the most common primary central nervous f

Temporal lobe Amnesia System Tumors Dominant Aphasia Meningiomas hemisphere Meningioma is the most common primary central nervous f | #Symptoms of elevated intracranial pressure include nausea, vomiting, blurry | system (CNS) tumor. Often found incidentally, meningiomas | vision, papilledema, and inability to abduct the eyes (bilateral abducens nerve are benign dural-based tumors that typically show homoge- | [cranial nerve VI] palsy). L umnemes ne ee 4 nous enhancement on postcontrast MRI. They have a smooth, 87