266 Chapter 7 2 Rheumatoid arthritis ◆ Common disorder affecting 2–5% of the general population. ◆ Peripheral neuropathies occur in up 10% of patients. ◆ Neuropathies can be compressive secondary to infl ammation and fi brosis, or symmetric, sensory, distal polyneuropathy, mononeuropathy/mononeuropa- thy multiplex, and fulminant sensorimotor polyneuropathy due to vasculitis or vascular occlusion. 3 Vasculitis ◆ Spectrum of disorders characterized by infl ammation of blood vessels and resultant luminal occlusion with downstream tissue ischemia. ◆ Peripheral nerve involvement is common. ◆ Broadly characterized as systemic necrotizing vasculitis, hypersensitivity vas- culitis, giant cell arteritis, or localized vasculitis. 4 Sarcoidosis ◆ Multisystem granulomatous disorder. ◆ 5% of patients have neurological manifestations. ◆ Cranial neuropathies are the most common neurological manifestation (73%). ◆ Additional neurological manifestations include: multiple motor/sensory mononeuropathies, polyradiculoneuropathies, cauda equina syndrome, and symmetric sensorimotor neuropathy. 5 Amyloidosis ◆ Multisystem disorder characterized by extracellular deposition of β-pleated sheet fi brillar proteins. ◆ Usually presents after age 40, men affected 2:1 over women. ◆ Peripheral neuropathy present in 10–35% of patients. ◆ Clinical symptoms include painful dysesthesias with decrement in spinotha- lamic modalities, carpal tunnel syndrome, and dysautonomia. 6 Systemic sclerosis ◆ Connective tissue disease characterized by excessive collagen deposition. ◆ Neurological complications include myopathies but are uncommon. Infl ammatory demyelinating polyradiculopathies • Acquired, immune-mediated, demyelinating diseases characterized primarily by their clinical course as chronic or acute. • Acute forms, with maximal defi cits occurring within 4 weeks of illness, are classifi ed as Guillain-Barré syndromes. • Disease with chronic progression or multiple relapses is classifi ed as chronic infl ammatory demyelinating polyradiculopathy (CIDP). Infectious, Infl ammatory, and Demyelinating Disorders 267 1 Guillain-Barré syndrome ◆ Annual incidence is approximately 1.8/100,000 ◆ Antecedent illness reported in 2/3 of patients ◆ Presentation includes parasthesias, sensory symptoms, and weakness ◆ Weakness distal and symmetric, with ascending progression ◆ Hypo/arefl exia invariably present ◆ Dysautonomia common ◆ Syndromes ■ Acute infl ammatory demyelinating polyradiculopathy (AIDP) ■ Acute motor axonal neuropathy ■ Acute motor/sensory axonal neuropathy ■ Miller-Fisher syndrome ■ Ophthalmoplegia and ataxia predominate ■ Associated with α-GQ1b antibodies 2 Chronic infl ammatory demyelinating polyradiculopathy (CIDP) ◆ Similar features with motor predominance and chronic progression or relaps- ing/remitting course Infl ammatory myopathies Signs/symptoms Childhood dermatomyositis Adult dermatomyositis Polymyositis Inclusion body myositis Pattern of weakness Proximal dysphagia Proximal dysphagia Proximal dysphagia Proximal distal dysphagia Presence of myalgia >50% <25% <10% Rare Skin involvement Periorbital edema, rash Periorbital edema, rash None None Joint involvement Contractures Contractures Rare None Other systems involved Rare Heart, lung Heart, lung None Other characteristics Onset typically after age 20 Male predominance, onset typically after age 50 • Characterized by disease of muscle in which infl ammatory cells are a prominent feature. • Hallmark features include generalized myalgias and muscle weakness. • Electrodiagnostic studies are helpful in establishing diagnosis. • Deep tendon refl exes are typically preserved out of proportion to weakness. • Etiology is poorly understood. • Treatment includes steroids and immunosuppressants. 268 Chapter 8 Peripheral Neurology General approach 269 Neuropathy vs. myopathy vs. ALS 269 Peripheral neuropathy: distribution of fi ndings 270 Peripheral neuropathy: temporal profi le 270 Primarily motor involvement 271 Rapidly progressive weakness 272 Acute weakness with minimal sensory symptoms 272 Plasmapheresis vs. intravenous immunoglobulins 274 Chronic weakness with minimal sensory symptoms 275 Mixed sensorimotor neuropathy (subacute/chronic) 277 Sensorimotor neuropathies associated with systemic disease 278 Sensorimotor neuropathies associated with medications/drugs 278 Sensorimotor neuropathies associated with toxins 279 Sensorimotor neuropathies associated with genetics (see Chapter 12: Neurogenetics) 279 Primarily sensory neuropathy 279 Primarily sensory neuropathies associated with systemic disease 280 Primarily sensory neuropathies associated with drugs/medications 281 Primarily sensory neuropathies associated with toxins 281 Primarily sensory neuropathies associated with genetics (see Chapter 12: Neurogenetics) 281 DDx by etiology 281 Cardiovascular manifestations in neuromuscular disorders 281 Hereditary neuropathies (see Chapter 12: Neurogenetics) 282 Neurological Differential Diagnosis: A Prioritized Approach Roongroj Bhidayasiri, Michael F. Waters, Christopher C. Giza, Copyright © 2005 Roongroj Bhidayasiri, Michael F. Waters and Christopher C. Giza Peripheral Neurology 269 Neuropathies with autonomic nervous system involvement 282 Neuromuscular disorders in the critically ill 283 Neuropathies associated with diabetes 284 Neuropathies associated with HIV/AIDS 285 Myopathies associated with normal creatine kinase 285 Myopathies associated with markedly elevated serum creatine kinase 286 Specifi c mononeuropathies and look-alikes 287 Median nerve disorders 287 Radial nerve disorders 288 Ulnar nerve disorders 289 Ulnar neuropathy vs. cervical radiculopathy 290 Meralgia paresthetica 291 Peroneal nerve disorders 291 Foot drop 292 Unilateral foot drop 293 Bilateral foot drop 293 General approach Neuropathy vs. myopathy vs. ALS Physical fi ndings Signs Neuropathy Myopathy ALS Atrophy Yes Yes Yes Distribution of weakness Distal Proximal Distal, bulbar Fasciculations Yes No Yes Sensory loss Yes No No Refl exes Hypoactive Maybe hypo Hyperactive Babinski sign No No Yes • Careful physical examination of the patient with weakness will quickly suggest whether the pattern is neuropathic, myopathic, or consistent with ALS (amyotrophic lateral sclerosis; motor neuron disease). • Six items to examine clinically include: atrophy, distribution of weakness, fasciculations, sensory loss, deep tendon refl exes, and plantar response. 270 Chapter 8 Diagnostic tests Tests Neuropathy Myopathy ALS Nerve conduction Slow Normal Normal Electromyography Fibrillations, large motor units Small motor units Giant motor units CSF protein May be elevated Normal Normal Muscle enzymes Normal Often elevated May be elevated Muscle biopsy Group atrophy Degeneration of muscle fi bers Group atrophy Peripheral neuropathy: distribution of fi ndings Focal Multifocal (asymmetric) Diffuse (symmetric) Mononeuropathy Monoradiculopathy Plexopathy Multiple mononeuropathy (Mononeuritis multiplex) Polyradiculopathy Motor neuropathy Motor neuronopathy Polyneuropathy Dorsal root ganglionopathy Motor neuronopathy Peripheral neuropathy: temporal profi le • Peripheral nerve disorders are characterized as being focal, multifocal (asymmetric), or diffuse (symmetric). • Most acquired neuropathies evolve symmetrically, initially with sensory disturbances in the feet that gradually ascend, referred to as a length- dependent or dying-back neuropathy. • Neuropathy that begins in one leg or hand usually indicates an asymmetric disorder. • The temporal evolution of the neuropathy is diagnostically helpful and directs the acuity of investigations and management. • Physicians should defi ne the time from onset to nadir or from onset to the current state as being acute (days to weeks), subacute (6 weeks to 6 months), or chronic (6 months to years). • The clinical course should also be described as being monophasic, progressive, or relapsing-remitting. • The temporal differentials below presume that the cause of sensorimotor dysfunction has been determined to be neuropathic. For predominantly motor impairment, it is important to consider non-neuropathic processes such as acute central lesions, disorders of the neuromuscular junction, and myopathies. Peripheral Neurology 271 Acute Axonal Demyelinating Alcohol Vasculitis Acute axonal neuropathy Toxins (thallium, arsenic, etc.) GBS HIV-AIDP Diphtheria Subacute/chronic Axonal Demyelinating Diabetes Uremia Alcohol Vitamin defi ciency HIV Medications Gastric surgery Hypothyroidism Connective tissue disease (SLE, Sjögren, etc.) Paraneoplastic Toxins (arsenic, etc.) CIDP Monoclonal gammopathy Hereditary (CMT, etc) Hypothyroidism Diabetes Medications Primarily motor involvement • Rapidly progressive weakness is a relatively common neurological presentation. • Primary motor neuropathies will present with muscle weakness and minimal, if any, sensory loss or impairment. However, non-neuropathic processes such as myopathies, neuromuscular junction disorders, and even acute central lesions must be considered. • Deep tendon refl exes are often diminished or absent. • Differential diagnosis can be divided into acute (hours/days) or chronic (weeks/months) duration of symptoms. • Neuropathic weakness tends to be more distal. Weakness due to myopathy or neuromuscular junction disorders is more proximal. • Multifocal neuropathies may have characteristic distributions, for example temperature-dependent distribution in lepromatous neuropathy. Pure or predominant sensory neuropathy is unlikely to be multifocal in distribution. 272 Chapter 8 Rapidly progressive weakness Features Botulism GBS MFS MG Tick paralysis Weakness Descending, fatigable Ascending Ascending Fatigable Ascending Refl exes Depressed in 50% Arefl exia or depressed Arefl exia or depressed Normal Arefl exia or depressed Ataxia Maybe No Yes No Maybe Ophthalmo- plegia Yes No Yes Yes and variable No Pupils Fixed, sluggish response Normal Normal Normal Normal Paresthesia or pain No Yes Some No No Autonomic dysfunction Yes Some Some No No CSF protein Normal Increased Increased Normal Normal Neuro- physiology Normal NCV, small MAP, unchanged on rep. stim. Slow or no potentiation of MAP with rep. stim. Slow or no potentiation of MAP with rep. stim. Decrement of MAP on rep. stim. Small MAP, absence or prolonged latencies Tensilon test Weakly positive Negative Negative Positive Negative Serum antibodies Clostridium botulinum Antiganglioside antibody Antiganglioside antibody Antiacetylcholine receptor antibody None GBS – Guillain-Barré syndrome, MFS – Miller-Fisher syndrome, MG – myasthenia gravis, NCV – nerve conduction velocity, MAP – motor action potential. Acute weakness with minimal sensory symptoms • Acute myelopathy, neuromuscular junction disorders, periodic paralysis, and other acute myopathies may mimic acute motor neuropathy. • The greatest concern with ACUTE WEAKNESS is the progression to respiratory failure. Vital capacity must be monitored and artifi cial ventilation initiated if necessary. • Many causes of acute motor weakness are treatable, so many less common causes are still important to consider. Peripheral Neurology 273 1 Guillain-Barré syndrome (GBS)/acute infl ammatory demyelinating polyneu- ropathy (AIDP) ◆ Worldwide incidence (0.4–1.7/100,000), often preceded by viral illness. ◆ Ascending symmetric paralysis with minimal sensory symptoms. Hypotonia, hypo/arefl exia, autonomic disturbances. May progress to respiratory failure. Facial diplegia and ophthalmoplegia variants. ◆ CSF: increased protein, acellular. Nerve conductions slowed. ◆ Respiratory support if needed. Treatment includes plasma exchange or intra- venous immunoglobulin. ◆ An acute axonal form of GBS has been described. ◆ Clinically mimicked by polyneuropathy/neuritis associated with AIDS, infec- tious mononucleosis. or viral hepatitis. 2 Acute myelopathy (can present with arefl exia and para- or quadriparesis) 3 Neuromuscular disease 3.1 Myasthenia gravis ■ Clinical characteristics: fl uctuating weakness, muscle fatigability, ocular/ cranial nerve muscles affected, then neck and limbs. ■ Myasthenic ‘crisis’ with respiration and oropharyngeal muscle weakness; precipitated by intercurrent illness, surgery, or occurs spontaneously. ■ EMG: decremental response to repetitive stimulation; increased jitter. 3.2 Drug-induced: aminoglycoside and polypeptide antibiotics; possibly worse with concomitant renal failure and steroid use. ■ Most severe: neomycin, colistin > moderate: kanamycin, gentamicin, streptomycin, tobramycin, amikacin > negligible effects: tetracycline, erthyomycin, vancomycin, clindamycin 4 Poliomyelitis: incidence (0.01/100,000), very rare ◆ Fever, headache, abdominal pain, paralysis (usually asymmetric), meningis- mus. Bulbar variant. ◆ CSF: aseptic meningitis. Increased WBCs, protein. 5 Botulism ◆ Food poisoning due to toxin released by Clostridium botulinum. ◆ Initial symptoms: blurred vision, unreactive pupils, ptosis, diplopia, ophthal- moplegia, bulbar paralysis. Followed by respiratory failure and weakness of limbs and trunk. Constipation. ◆ Treat with trivalent botulinum antiserum. 6 Diphtheria ◆ Due to toxin produced by Corynebacterium diphtheriae. ◆ Infl ammatory pharyngitis. Cardiac and neurological involvement in 20%. ◆ 1–2 weeks: palatal paralysis, cranial neuropathies, ciliary paralysis, blurred vision; however, external ophthalmoplegia rare. 274 Chapter 8 ◆ 5–8 weeks: sensorimotor polyneuropathy, may be GBS-like. ◆ Acutely, treatment with antitoxin. No effective treatment for neuropathy. 7 Myopathy 7.1 Periodic paralysis: familial, weakness may lead to respiratory failure. ■ Hypokalemic. Attacks may be precipitated by cold, ingestion of food. Associated with thyrotoxicosis, GI loss, renal loss. ■ Hyperkalemic. Attack precipitated by cold or high potassium. 7.2 Acute polymyositis (see Chronic weakness, p. 276). 7.3 Acute steroid-induced myopathy. 8 Porphyric polyneuropathy (acute intermittent porphyria) ◆ Autosomal dominant inheritance. Attacks triggered by many drugs. ◆ Abdominal pain, psychosis (delirium), seizures, predominantly motor polyneuropathy. Respiratory failure can occur. Autonomic symptoms. ◆ Urine porphobilinogen elevated (turns dark when standing). 9 Other viral: other enteroviruses, West Nile virus. 10 Acute uremic polyneuropathy: can mimic GBS/AIDP ◆ Associated with end-stage renal failure and diabetes. 11 Acute toxic motor polyneuropathy ◆ Triorthocresylphosphate, other organophosphates, thallium salts. ◆ Less often: arsenic polyneuropathy, eosinophilia-myalgia syndrome due to contaminated L-tryptophan. 12 Tick paralysis ◆ Toxin produced by feeding tick. History of outdoor activity, insect bites. More often in children. ◆ Ascending paralysis that may progress to bulbar and respiratory weakness. ◆ Search for and remove tick. 13 Vasculitic: systemic lupus erythematosis, polyarteritis nodosa. 14 Paraneoplastic (occult carcinoma, Hodgkin) 15 Alcoholism ◆ May present with subacute axonal motor neuropathy Plasmapheresis vs. intravenous immunoglobulins • Both plasmapheresis (or plasma exchange) and intravenous immunoglobulin (IVIg) are effective treatment in various neuromuscular disorders. Both treatments have been shown to be equally effective in the treatment of Guillain-Barré syndrome. • In addition to the underlying disorder and patient’s general condition, the decision to choose either plasmapheresis or IVIg also depends on potential side-effects. Most commonly, both treatments are administered to patients who are critically ill in the intensive care setting, with IVIg being better tolerated by patients with impaired hemodynamics. Peripheral Neurology 275 Features Plasmapheresis Intravenous immunoglobulin Dose 40–50 ml/kg of plasma is removed, replacing the plasma with albumin or saline. A series of 3–6 exchanges on a daily or alternate-day regime is often administered 2 g/kg, divided into 2–5 daily infusions Side-effects Flu-like illness (most common, particularly in patients with reduced immunoglobulin levels) Hemodynamic instability • Cardiac arrthymias • Orthostatic hypotension • Autonomic dysfunction Venous access complications • Bleeding • Thrombophlebitis • Line infections • Pneumothorax Coagulopathy • Prolonged PT • Prolonged PTT • Thrombocytopenia Electrolyte imbalance • Hypocalcemia • Hypomagnesemia Flu-like illness (most common) Vascular-like headache Atrial and venous thrombosis Pulmonary embolism Hypertensive encephalopathy Leukopenia Worsening renal failure Electrolyte imbalance • Hypocalcemia • Hyponatremia IgA anaphylaxis (serum IgA measurement is required before therapy) Cerebral symptoms • Delirium • Cortical blindness • Seizures Retinal necrosis Hepatitis C (rare) PT – prothrombin time, PTT – partial thromboplastin time. Chronic weakness with minimal sensory symptoms • Common indications for plasmapheresis or IVIg include: ◆ Guillain-Barré syndrome ◆ Myasthenia gravis (during attack or crisis) ◆ Lambert-Eaton myasthenic syndrome ◆ Chronic infl ammatory demyelinating polyneuropathy (CIDP) ◆ Some infl ammatory myopathies ◆ Paraneoplastic syndromes • Neuromuscular disease, myopathy, and motor neuron disease can present with LOWER MOTOR NEURON signs and mimic chronic motor neuropathy. • Examination fi ndings consistent with chronic motor disorders include atrophy, fasciculations, and reduced refl exes. Spontaneous fasciculations tend to be more prominent in chronic neuropathies or motor neuron disease than in myopathies or neuromuscular junction disorders. [...]... neuron disease 6 Bilateral parasagittal lesions Neurological Differential Diagnosis: A Prioritized Approach Roongroj Bhidayasiri, Michael F Waters, Christopher C Giza, Copyright © 2005 Roongroj Bhidayasiri, Michael F Waters and Christopher C Giza Chapter 9 Neuro-ophthalmology and Neuro-otology Cardinal positions of gaze 295 Ocular problems 2 96 Pupillary abnormalities Fixed dilated pupil Argyll-Robertson... reactive, loss of consensual response ◆ Due to lesions in optic nerve, chiasm: multiple sclerosis, optic neuritis 6 Others 6. 1 Amyloidosis; due to associated autonomic neuropathies 6. 2 Bilateral optic atrophy 6. 3 Brainstem encephalitis, Miller-Fisher variant of Guillain-Barré syndrome 6. 4 Lyme disease 6. 5 Wernicke encephalopathy, chronic alcoholism ■ ■ ■ ■ Relative afferent pupillary defect • The swinging... the light-reflex pathway; ventral to the Edinger-Westphal nuclei Unlike the light-reflex pathway which is entirely subcortical, the near-reflex pathway sends fibers to the cortex bilaterally 298 Chapter 9 1 Diabetes mellitus ◆ Probably the most common cause of light-near dissociation due to presumed small vessel disease 2 Dorsal midbrain syndrome (Parinaud syndrome) ◆ Physical signs include: Mid-dilated... dystrophy • Emery-Dreifuss muscular dystrophy • Limb-girdle type 1B, 1D, 2C, 2E, 2F muscular dystrophy • • • • Myotonic dystrophy • Intraventricular conduction defect, mainly right or left bundle branch block (due to fatty infiltration of the Purkinje-His system) • Stoke-Adams syndrome • Heart failure in 10% of cases Friedreich ataxia • Hypertrophic > dilated cardiomyopathies Charcot-Marie-Tooth disease... component to both 10.1 HMSN I (Charcot-Marie-Tooth): hypertrophic demyelinating 10.2 HMSN II: axonal 11 Diabetes: purely motor involvement occurs but is very rare Mixed sensorimotor neuropathy (subacute/chronic) • • • • • • • Very large differential diagnosis Most sensorimotor neuropathies occur over a subacute to chronic (weeks/ months) time course May divide differential by etiology, associated with:... to 0.05–0.1% with pilocarpine eye drops, which affect a normal pupil only minimally Neuro-ophthalmology and Neuro-otology 297 4 Others 4.1 Traumatic sphincter iris rupture 4.2 Acute angle-closure glaucoma Argyll-Robertson pupil • • • • Pupils are small, irregular, and unequal Normal afferent visual system Light-near dissociation: light reflex is absent, but accommodation and convergence are intact Little... Sensorimotor neuropathies associated with medications/drugs 1 Anti-infectives Peripheral Neurology 279 1.1 Isoniazid: may induce vitamin B6 deficiency; usually sensory 1.2 Nitrofurantoin: dose-dependent; exacerbated by renal failure 1.3 Thalidomide 2 Chemotherapeutic agents 2.1 Vincristine 3 Antiarrhythmics 3.1 Amiodarone: dose-dependent 3.2 Perhexilene dose-dependent 4 Miscellaneous 4.1 Aurothioglucose: idiosyncratic... upper extremity > lower weakness, asymmetric ◆ Responds to immunosuppressive therapy (IVIg, cyclophosphamide) ■ ■ ■ ■ ■ ■ ■ Peripheral Neurology 277 6 Toxins 6. 1 Lead: focal weakness of hand/wrist extensors 6. 2 Dapsone: dose-related motor neuropathy 7 HIV-associated motor neuropathy: can mimic CIDP 8 Paraproteinemia (multiple myeloma, osteosclerotic myeloma, MGUS – monoclonal gammopathy of uncertain... 3 Alcohol-related (toxin, also associated vitamin deficiency and liver disease) 4 Vitamin deficiencies 4.1 Vitamin B1 (thiamine) deficiency: burning dysesthesias feet > hands, wasting of distal > proximal muscles; axonal neuropathy 4.2 Vitamin B12 deficiency: subacute combined degeneration, impaired proprioception/vibration, painful paresthesias 5 Chronic liver disease 6 Paraneoplastic 6. 1 Lung 6. 2 Lymphoma... Syringobulbia 5.3 Chronic alcoholism Any chronic lesions involving the rostral midbrain can cause Argyll-Robertson pupil Horner syndrome (see Chapter 2: Clinical syndromes) Light-near dissociation • • Light-near dissociation refers to an absent or impaired light reflex with preserved accommodation and convergence The near-reflex pathway subserves pupillary constriction when fixating at a close target The final common . subacute (6 weeks to 6 months), or chronic (6 months to years). • The clinical course should also be described as being monophasic, progressive, or relapsing-remitting. • The temporal differentials. saline. A series of 3 6 exchanges on a daily or alternate-day regime is often administered 2 g/kg, divided into 2–5 daily infusions Side-effects Flu-like illness (most common, particularly in patients. B 12 defi ciency. Peripheral Neurology 277 6 Toxins 6. 1 Lead: focal weakness of hand/wrist extensors 6. 2 Dapsone: dose-related motor neuropathy 7 HIV-associated motor neuropathy: can mimic CIDP