Neurological Emergencies - part 9 pot

and on maximal inspiration (± measurement of the diaphragmatic EMG). Alternatively magnetic stimulation of the phrenic nerves may be used to assess diaphragmatic contractility. However, neither of these tests is routinely performed outside research centres. Diagnosis of the cause Central nervous system causes Diseases of the nervous system can cause respiratory failure by damaging the respiratory centre in the medulla or its connections with the cervical and thoracic spinal cord (Box 11.1). In practice the commonest causes are the secondary consequences of CNS depression by drugs, metabolic abnormalities, or primary cerebral or brain stem disease. These are important in differential diagnosis but this review is confined to disorders affecting the lower motor neuron, peripheral nerves, neuromuscular junction, and muscles. The ACUTE NEUROMUSCULAR RESPIRATORY PARALYSIS 381 Box 11.1 Central nervous system disorders causing respiratory failure Sedative drugs Secondary effects of metabolic disorders Central transtentorial herniation Brain stem lesions Infarction Haemorrhage Extrinsic compression Intrinsic tumour Encephalitis Multiple sclerosis Motor neuron disease Central pontine myelinolysis Spinal cord lesions Cord compression Motor neuron disease Intrinsic tumour Multiple sclerosis Transverse myelitis Poliomyelitis Rabies localisation of the disease process to the brain stem or spinal cord does not usually present the neurologist with any difficulty because of the presence of symptoms and signs at the level of the lesion and involvement of the long tracts. Wild type poliomyelitis remains a common problem in the Indian subcontinent and south east Asia. Rare vaccine- associated cases still occur throughout the world. Poliomyelitis should still be considered in the differential diagnosis of acute flaccid paralysis when sensory deficit is absent, the onset is asymmetrical, and the CSF shows a pleocytosis especially in recent vaccine recipients or their contacts. 7,8 Enteroviruses other than polio and flaviviruses which cause tick-borne encephalitis can also produce a poliomyelitis-like illness. 9 The diagnosis of polio may be confirmed by culturing the stool, and sometimes a throat swab or CSF, and by finding a rising titre of neutralising antibody in the serum. Peripheral neuropathy Peripheral neuropathy causing respiratory failure can usually be identified clinically from the gradual evolution of ascending, or sometimes descending, weakness associated with paraesthesiae, sensory deficit, and reduced or absent tendon reflexes. Difficulties in diagnosis arise in rapidly evolving pure motor neuropathies, especially in the earliest stages when the tendon reflexes may be preserved. Also paraesthesiae occur in occasional cases of toxic neuromuscular conduction block, including botulism. 10 Guillain–Barré syndrome is so much more common than any of the other causes of neuromuscular respiratory failure that there is a danger that other causes, including other causes of neuropathy, will be overlooked. The diagnosis of GBS cannot be made by any diagnostic test but requires the exclusion of other conditions (Table 11.1). The diagnosis of GBS itself is no longer sufficient since it is now recognised to be a syndrome with several underlying pathological processes. 11 In Europe and North America over 90% of cases are due to acute inflammatory demyelinating polyradiculoneuropathy and the remainder to acute motor or motor and sensory axonal neuropathy. 12 In northern China, Japan, India, and Central America the axonal forms of the disease are more common, accounting for up to 40% of cases. The distinction during life NEUROLOGICAL EMERGENCIES 382 is difficult and depends on careful neurophysiological studies. In acute inflammatory demyelinating polyradiculoneuropathy there is multifocal partial conduction block or slowing of motor nerve conduction. In the axonal forms there is a reduction of compound muscle action potential amplitude with relative preservation of motor nerve conduction velocity. 11–13 In very severe cases the action potentials may be unrecordable in which case the diagnosis can only be made by biopsy of an affected nerve. This is not worth performing except in a specialist centre. The other causes of neuropathy (Table 11.1) can be ruled out by a careful history. Critical illness polyneuropathy occurs in the setting of an extremely ill patient who is being ventilated, has had sepsis and multiorgan failure, and cannot be weaned from the ventilator. It is due to an axonal neuropathy. The aetiology of critical illness polyneuropathy is not known but probably multifactorial. 14 Careful enquiry about possible toxin exposure as a cause of polyneuropathy is always necessary. Acute ingestion of organophosphorus compounds is often due to attempted suicide and usually causes vomiting. After one to five days, as survivors emerge from coma, some develop acute paralysis with respiratory failure. This is called the “intermediate syndrome” to distinguish it from the later organophosphate induced delayed sensory and motor polyneuropathy which organophosphates may also cause. Electromyography shows pre- and postsynaptic impairment and the intermediate syndrome is probably due to necrosis of the neuromuscular junctions. 15 The majority of patients with the intermediate syndrome recover spontaneously provided they do not suffer hypoxic brain injury. Inadequate pralidoxime therapy is proposed but not established as contributory. Poisoning with heavy metals severe enough to cause a neuropathy with respiratory failure has usually been preceded by an acute illness with vomiting and an altered level of consciousness often misdiagnosed as viral illness. Prominent cutaneous and muscular pain, especially in the soles of the feet, and preservation of the reflexes in the early stages should raise the suspicion of thallium poisoning. 16 Painful tingling and weakness begin within one to five days from ingestion of thallium, before the characteristic hairfall. In arsenic poisoning, sensory symptoms such as pins and needles predominate early, and weakness may then develop. ACUTE NEUROMUSCULAR RESPIRATORY PARALYSIS 383 NEUROLOGICAL EMERGENCIES 384 Table 11.1 Peripheral neuropathies that cause respiratory failure Condition Specific test Specific treatment GBS (demyelinating from) Nerve conduction block IVIg PE GBS (axonal form) Small CMAPs IVIg PE Relatively normal MCV CIDP Nerve conduction block IVIg PE S Nerve biopsy Critical illness polyneuropathy 14 Toxins Organophosphorus Red cell cholinesterase* Atropine compounds 94 Blood OP Pralidoxime Urine OP Thallium 95 Dystrophic anagen hairs with dark bands 95% sensitive and specific for thallium poisoning Whole blood thallium Prussian blue 24 hour urine thallium Arsenic 17,96–98 24 hour urine arsenic Dimercaprol Whole blood arsenic † DMSA Lead Whole blood lead Sodium calcium edetate DMSA Gold 99 Dimercaprol Lithium 100,101 Plasma lithium Haemodialysis Drugs: Vincristine 21,102 Withdrawal Lymphoma 103 Nerve biopsy Cytotoxics Vasculitis: systemic Nerve biopsy S cyclophosphamide lupus erythematosus 104 IVIg? Metabolic: acute Urine porphobilinogen Avoidance of intermittent porphyria 23 Urine d-ALA precipitants Intravenous haematin Hereditary tyrosinaemia 25 High calorie intake Liver transplant Diphtheria 105 Throat swab culture Antitoxin Buckthorn neuropathy (central America) 20,106 GBS = Guillain–Barré syndrome; PE = plasma exchange; IVIg = intravenous immunoglobulin; CIDP = chronic idiopathic demyelinating polyradiculoneuropathy; S = steroids; CMAPs = compound muscle action potentials; MCV = maximum conduction velocity; OP = organophosphorus d-ALA = d-aminolaevulinic acid; Prussian blue = potassium ferric hexacyanoferrate; DMSA = 2,3- dimercaptosuccinic acid. * An isolated cholinesterase level may neither confirm nor exclude exposure because a normal cholinesterase level is based on population estimates. Ideally the diagnosis is based on a drop of 50% from baseline cholinesterase determinations. Animal studies have suggested in intermediate syndrome that AchE must be 20% or lower before muscle activity is affected. † An elevated arsenic level verifies the diagnosis whereas a low level does not exclude arsenic toxicity. Seafood ingestion may transiently increase arsenic levels too. The early clinical picture sometimes closely resembles GBS and neurophysiological changes may initially show partial conduction block and slowing of conduction before giving way to changes suggestive of axonal degeneration. 17 Diphtheria is now extremely rare in Europe and North America but cases were recently reported from Estonia 18 and the diagnosis should be considered in patients with a recent upper respiratory infection, especially if there is prominent palatal involvement. 19 Buckthorn neuropathy need only be suspected in those who have consumed berries from this bush in Mexico. 20 Drugs usually cause an insidiously progressive distal axonopathy without respiratory involvement, but acute paralysis with respiratory failure occurred in a patient being treated with vincristine, possibly due to coincidental GBS. 21 Both T and B cell lymphomas may cause acute neoplastic infiltration of the peripheral nervous system which can resemble GBS. 22 Sometimes acute neuropathy is the presenting feature of the lymphoma. Vasculitic neuropathy rarely causes respiratory failure and usually only does so in the setting of a systemic illness with cutaneous, renal, and lung involvement. Acute neuropathy occurs in acute intermittent porphyria, usually after abdominal pain and vomiting, but sometimes as the presenting feature. 23 It may be diagnosed during attacks by detecting increased urine porphobilinogen excretion, a test which should be considered in every case of undiagnosed acute neuromuscular paralysis. 24 Recurrent neuropathy in infants is a feature of hereditary tyrosinaemia. 25 Neuromuscular junction disorders Respiratory failure can herald disorders of the neuromuscular junction (Table 11.2), which can be distinguished from neuropathic causes by the absence of sensory deficit and preservation of tendon reflexes. In myasthenia gravis respiratory failure usually occurs in the setting of established disease that has failed to respond to conventional treatment. Even in an acute case the diagnosis is usually evident because of ptosis, facial weakness, and bulbar palsy with muscle fatigue. The diagnosis can be confirmed by showing a decrement in the compound muscle action potentials elicited by a train of stimuli, neurophysiological tests, or detecting variable conduction block (jitter) in terminal motor nerve fibres in ACUTE NEUROMUSCULAR RESPIRATORY PARALYSIS 385 almost all cases. Acetylcholine receptor antibodies are present in 90% of patients and in about half of the remainder there are antibodies to the muscle specific kinase, which is closely apposed to the acetylcholine receptor. 26 The rare occurrence of asystole following intravenous edrophonium has led some experts to stop using it. If it is used, atropine should be given first and resuscitation facilities should be available. In treated myasthenia, weakness can be caused by overdose of anticholinesterase drugs causing depolarisation of motor nerve terminal in a cholinergic crisis. This will be accompanied by NEUROLOGICAL EMERGENCIES 386 Table 11.2 Disorders of neuromuscular transmission that cause respiratory failure Condition Specific test Specific treatment Myasthenia gravis Single fibre EMG IVIg, PE, S for jitter Anti AChR antibody Edrophonium test * Anticholinesterase Negative edrophonium Drug withdrawal overdose test Antibiotic induced Drug withdrawal paralysis 107 Hypermagnesaemia 28 Plasma magnesium Intravenous calcium EMG increment on 50 Hz stimulation Botulism 27 Injection of serum Antitoxin into mice Snake, scorpions, Identifying the snake Antivenin and spider bite 108 or its venom † Fish, shellfish, crab Identifying the fish Varies poisoning 31,32,108 Tick paralysis 33 Finding the tick Removal/antitoxin depending on tick species Eaton–Lambert EMG increment on PE, S syndrome 34 repetitive stimulation Anti VGCC antibody PE = plasma exchange; S = steroids; AChR = acetylcholine esterase receptor; VGCC = voltage gated calcium channel. * This runs the risk of fatal bradycardia and should only be performed by an experienced clinician after giving atropine and in an intensive care setting. † Kits are now available to detect some snake venoms (especially in Australia) and allow the most appropriate antivenin to be chosen. diarrhoea, colic, excessive salivation, and small pupils, and will be worsened rather than improved by intravenous edrophonium. Other causes of neuromuscular junction blockade are rare and the diagnosis is usually obvious from the clinical setting. Suspect botulism when autonomic features, dry mouth, constipation, poorly reactive pupils, ptosis, and bulbar palsy have heralded acute descending paralysis. In the early stages the symptoms and signs are entirely anticholinergic and the reflexes are normal. These symptoms have usually been immediately preceded by nausea, vomiting, abdominal pain, and diarrhoea from eating foul smelling food contaminated by Clostridium botulinum. 27 Magnesium- containing antacids and aperients in patients with impaired renal function can produce severe hypermagnesaemia. The increased magnesium interferes with the release of acetylcholine so as to cause weakness, which may develop into respiratory failure. 28 The aminoglycoside and polymyxin antibiotics and some other drugs also cause neuromuscular blockade by interfering with the release of acetylcholine. 29 This is usually only significant when weaning infected patients off ventilation. 30 Physicians practising in the tropics have to cope with a much wider range of toxic causes of neuromuscular conduction blockade whose diagnosis will be obvious from the history (Table 11.2). 31 Fish or shellfish toxin poisoning (usually Caribbean or Pacific fish) causes a gastrointestinal upset before the development of weakness. 32 In North America paralysis is sometimes caused by the bite of a female tick, Dermacentor spp., whose saliva contains an unidentified toxin which interferes with terminal motor nerve conduction perhaps by inhibiting sodium flux across the axolemma. The tick may be difficult to find but its removal is curative. 33 In Australia tick paralysis caused by Ixodes holocyclus is due to a toxin which inhibits acetylcholine release and causes neuromuscular conduction block. Respiratory failure occurs in the Lambert–Eaton myasthenic syndrome, but only rarely and then usually in the setting of gradually progressive weakness. 34 The diagnosis may be suggested clinically by autonomic symptoms, including a dry mouth, the finding of depressed reflexes that are enhanced after exercise, and confirmed by electrophysiological tests showing an increment in muscle action potential amplitude following repetitive ACUTE NEUROMUSCULAR RESPIRATORY PARALYSIS 387 nerve stimulation. It may be associated with a small cell lung carcinoma or autoimmune disease. Myopathy Respiratory failure in muscle disease usually occurs insidiously following progressive proximal weakness, which has evolved over months or years, and presents with nocturnal hypoventilation causing morning headache and daytime sleepiness. This form of respiratory failure may develop in the advanced stages of severe muscular dystrophy and also in polymyositis. Sometimes, especially in myotonic dystrophy, the respiratory failure is worsened by depression of central respiratory drive. When the ventilatory reserve has fallen so far that the vital capacity is less than 55% of its predicted normal, there is a grave danger that an intercurrent lung infection will precipitate respiratory failure. 35 In acid maltase deficiency the diaphragm is particularly severely affected and the patient may present with respiratory failure before consulting a neurologist about weakness. 36 Acid maltase deficiency should be suspected if there is proximal upper limb weakness and marked wasting of the paraspinal muscles, and confirmed by seeking glycogen containing granules in the lymphocytes which stain red with periodic anti-Schiff reagent applied to a blood film. 37 Although rare, some muscle diseases may present with acute respiratory failure (Table 11.3). When a patient presents with flaccid paralysis and respiratory failure over a few hours or days, a correctable electrolyte disturbance should be sought immediately. The feature that distinguishes muscle disease from neuropathy is the preservation of the reflexes and the absence of sensory symptoms or signs. Hypokalaemia induced by potassium loss from the gut or kidneys is the commonest cause and is probably responsible for the muscle fibre necrosis in acute rhabdomyolysis, which occurs following some drugs, such as carbenoxolone. 38 Severe hypophosphataemia can also cause paralysis requiring respiratory failure. It is often precipitated by parenteral glucose infusions in alcoholic patients. 39 Acute rhabdomyolysis is a rare condition in which acute muscle necrosis causes the very rapid onset of muscle pain, tenderness, swelling, and weakness, sometimes severe enough NEUROLOGICAL EMERGENCIES 388 to cause respiratory failure. The muscle enzyme concentrations, including creatine kinase, are markedly increased in the plasma, and the electromyogram (EMG) shows myopathic changes and spontaneous fibrillation. A muscle biopsy is necessary to confirm the diagnosis and will show massive muscle fibre necrosis and often numerous regenerating fibres but relatively little inflammation. The neurological picture is overshadowed by the development of myoglobinuria and acute renal failure. Causes of acute rhabdomyolysis are alcohol abuse, viruses (influenza, Coxsackie B5, echo 9, adenovirus 21, Epstein–Barr), Mycoplasma, 40 and a wide variety of drugs, especially potassium-lowering drugs, amphetamine-like agents including Ecstasy (MDMA) and Speed (amphetamine sulphate), barbiturates, and the combination of the muscle relaxant pancuronium and corticosteroids. 41 If the causative agent is withdrawn and the patient can be nursed through the period of respiratory and renal failure, regeneration of the necrotic muscle and full recovery are usual. ACUTE NEUROMUSCULAR RESPIRATORY PARALYSIS 389 Table 11.3 Disorders of muscle that cause acute respiratory failure Condition Specific test Specific treatment Hypokalaemia 38,109 Plasma K + K + Polymyositis 110 Plasma CK S, IVIg EMG Muscle biopsy Acute rhabdomyolysis 87 EMG Urine alkalinisation Muscle biopsy Hypophosphataemia 39 Plasma phosphate Phosphate Acid maltase PAS stain of blood film deficiency 36,37 Combined Muscle biopsy Withdrawal neuromuscular blockade and steroids 111 Barium intoxication 112 Plasma K + Intravenous K + Oral magnesium sulphate haemodialysis Critical illness thick Muscle electron filament myopathy microscopy CK = creatine kinase; PAS = periodic acid-Schiff reagent. [...]... controlled trial of high-dose intravenous immune globulin infusions as treatment for dermatomyositis N Engl J Med 199 3;3 29: 199 3–2000 93 Esteban A, Alia I Clinical management of weaning from mechanical ventilation Intensive Care Med 199 8;24 :99 9–1008 94 Senanayave N, Johnson MK Acute polyneuropathy after poisoning by a new organophosphate insecticide N Engl J Med 198 2;306:155–7 95 Moore D, House I, Dixon... Trop Geographic Neurol 199 1;1:3–15 403 NEUROLOGICAL EMERGENCIES 32 Mills AR, Passmore R Pelagic paralysis Lancet 198 8;i:161–4 33 Felz MW, Smith CD, Swift TR A six-year-old girl with tick paralysis N Engl J Med 2000;342 :90 –4 34 Nicolle MW, Stewart DJ, Remtulla H, Chen R, Bolton CF Lambert–Eaton myasthenic syndrome presenting with severe respiratory failure Muscle Nerve 199 6; 19: 1328–33 35 Braun NM, Arora... N Post-operative feeding Br Med J 199 1;303:1007–8 56 Wilmore DW Catabolic illness – strategies for enhancing recovery N Engl J Med 199 2;325: 695 –702 57 Pingleton S Nutritional management of acute respiratory failure JAMA 198 7;257:3 094 9 58 Deitch EA The role of intestinal barrier failure and bacterial translocation in the development of systemic infection and multiple organ failure Arch Surg 199 0;125:403–4... patients receiving continuous mechanical ventilation Intensive Care Med 198 9;1 39: 877–84 69 Ruiz-Santana S, Garcia Jimenez A, Esteban A, et al ICU pneumonias: a multi-institutional study Crit Care Med 198 7;15 :93 0–2 70 Tuck RR, McLeod JG Autonomic dysfunction in Guillain–Barré syndrome J Neurol Neurosurg Psychiatry 198 1;44 :98 3 90 71 Tripathi M, Kaushik S Carbamezapine for pain management in Guillain–Barré... 199 9;67:433–8 19 Swift TR, Rivener MH Infectious diseases of nerve In: Matthews WB, ed Handbook of clinical neurology Amsterdam: Elsevier, 198 7;1 79 84 20 Calderon-Gonzalez R, Rizzi-Hernandez H Buckthorn neuropathy N Engl J Med 196 7;277: 69 71 21 Norman M, Elinder G, Finkel Y Vincristine neuropathy and a Guillain–Barré syndrome: a case with acute lymphatic leukemia and quadriparesis Eur J Haematol 198 7; 39: 75–6... syndrome Q J Med 198 8;68:735 9 51 Hazard P, Jones C, Benitone J Comparative clinical trial of standard operative tracheostomy with percutaneous tracheostomy Crit Care Med 199 1; 19: 1018–24 52 Friedman Y, Fildes J, Mizock B, et al Comparison of percutaneous and surgical tracheostomies Chest 199 6;110:480–5 53 Ciaglia P Percutaneous dilatational tracheostomy – results and long term follow-up Chest 199 2;101:464–7... Guillain–Barré syndrome: clinical associations and outcome Ann Neurol 199 8;44:780–8 13 Ho TW, Mishu B, Li CY, et al Guillain–Barré syndrome in northern China Relationship to Campylobacter jejuni infection and anti-glycolipid antibodies Brain 199 5;118: 597 –605 14 Bolton CF Critical illness polyneuropathy: a useful concept Muscle Nerve 199 9;22:4 19 22 15 Sedgwick EM, Senanayake N Pathophysiology of the intermediate... syndrome of organophosphorus poisoning J Neurol Neurosurg Psychiatry 199 9;62:201–2 16 Cavanagh JB, Fuller NH, Johnson HRM, Rudge P The effects of thallium salts, with particular reference to the nervous system changes Q J Med 197 4;43: 293 –3 19 17 Greenberg SA Acute demyelinating polyneuropathy with arsenic ingestion Muscle Nerve 199 6; 19: 1611–13 18 Logina I, Donaghy M Diphtheritic polyneuropathy A clinical... Med J 196 6;1: 1581–2 39 Newman JH, Neff TA, Ziporin P Acute respiratory failure associated with hypophosphatemia N Engl J Med 197 7; 296 :1101–3 40 Mastaglia FL, Ojeda VJ Inflammatory myopathies Ann Neurol 198 5;17:215–27,317–23 41 Sitwell LD, Weinshenker BG, Monpetit V, Reid D Complete ophthalmoplegia as a complication of acute corticosteroid- and pancuronium-associated myopathy Neurology 199 1;41 :92 1–2... Moore D, House I, Dixon A, et al Thallium poisoning Br Med J 199 3;306: 1527 9 96 Donofrio PD, Wilbourne AJ, Albers JW, Rogers L, Salanga V, Greenberg HS Acute arsenic intoxication presenting as Guillain–Barré like syndrome Muscle Nerve 198 7;10:114–20 406 ACUTE NEUROMUSCULAR RESPIRATORY PARALYSIS 97 98 99 100 101 102 103 104 105 106 107 108 1 09 110 111 112 Greenberg C, Davies S, McGowan T, Schorer A, Drage . muscle action potentials; MCV = maximum conduction velocity; OP = organophosphorus d-ALA = d-aminolaevulinic acid; Prussian blue = potassium ferric hexacyanoferrate; DMSA = 2, 3- dimercaptosuccinic. and -3 polyunsaturated fatty acids. 64 Tight control of blood sugar levels (target range 4·5–6 mmol/L) has also been shown to play an important part in reducing NEUROLOGICAL EMERGENCIES 394 morbidity,. blue 24 hour urine thallium Arsenic 17 ,96 98 24 hour urine arsenic Dimercaprol Whole blood arsenic † DMSA Lead Whole blood lead Sodium calcium edetate DMSA Gold 99 Dimercaprol Lithium 100,101 Plasma