Acute and Subacute Weakness

CME: CLINICAL PRACTICE AND ITS BASIS

patients may initiall y retain their reflexes but they should always disap- pear in established disease. The develop- Neurology ment of sphincter symptoms while the weakness is progressing raises the pos- sibility of cord disease and should be Edited by Geraint Fuller MD FRCP, appropriately investigated. Consultant Neurologist, Gloucester Royal Hospital The initial diagnosis of GBS is often made on clinical grounds. A lumbar puncture should be performed if there are no contraindications. An elevated protein level adds support to the diag- Acute and subacute and pain and temperature loss nosis, but may be normal during the first contralateral to the lesion – few days of symptoms. A cerebrospinal weakness Brown-Séquard syndrome) fluid leukocytosis (>10/mm 3) should root pain at the upper level prompt the search for an alternative sphincter involvement at diagnosis. Marguerite Hill MRCP DPhil, Consultant presentation Acute management involves careful Senior Lecturer in Neurology, Institute of a lower motor neurone ‘level’ monitoring of cardiac (rhythm and blood Clinical Neurosciences, Frenchay Hospital, (egweak elbow flexion and an pressure) and respiratory function. A Bristol absent biceps reflex). rising respiratory rate and falling forced vital capacity (FV C) (20 ml/kg) should Sensory levels may, however, be decep- Clin Med 2004;4:105–7 prompt an anaesthetic review. Peak flow tive, as the causative lesion may be much measurements and pulse oximetry are not higher than the level would suggest. The adequate. Deep vein thrombosis prophy- To be faced with a patient getting weaker physiological basis of this is not clear. If laxis is advisable. The rate of recovery is day by day or hour by hour is a daunting there is any suspicion that the patient increased by treatment with intravenous prospect. Accurate clinical assessment may have cord disease, urgent magnetic immunoglobulin (IVIg) 0.4 g/kg/day for of the patient is crucial (Table 1, Fig1) resonance is mandatory, imaging the five days or plasma exchange, 1,2 but the as the results of diagnostic tests may be spine from any motor or sensory level up effect on overall outcome has been disap- delayed for several days or be misleading to the top of the cervical spine. It is pointing. There is no evidence that steroid in the early stages of the disease. This important to be aware that high cervical treatment is beneficial. 3 article will review only the assessment, cord disease can result in respiratory investigation and management of failure from involvement of either the patients w ith spinal cord or neuro- phrenic nerve or the respiratory centres Vasculitic neuropathy muscular disease; weakness caused by in the upper cervical cord; such patients The classic presentation of vasculitis lesions above the foramen magnum will therefore require careful respirator y affecting the peripheral nervous system is be discussed in another paper in this monitoring. sequential dysfunction of individual section by Neil Scolding. peripheral nerves (mononeuritis multi- Peripheral neuropathies plex). However, where multiple nerves are Spinal cord disease Guillain-Barré syndrome being picked off with great rapidity the presentation can be a rapidly progressive, Diagnosing spinal cord pathology is rela- The typical patient with Guillain-Barré often extremely painful, distal neuropathy. tively easy if the patient presents with a syndrome (GBS) presents with rapidly Diagnostic clues include involvement of spastic paraparesis. However, acute progressive weakness that often starts other organs such as vasculitic skin spinal injury can initially present with proximally and may include the face, lesions, renal disease, an inflammatory flaccid weakness and areflexia, making absent reflexes and distal sensory dis- arthropathy, raised inflammatory markers differentiation from a polyneuropathy turbance. Many patients complain of or an eosinophilia. These conditions need difficult. The following features suggest a severe back pain that is thought to be to be treated quickly and aggressively with spinal cord lesion: secondary to root inflammation. It may high-dose parenteral steroids and cyclo- Lhermitte’s phenomenon (electric be possible to elicit a history of an upper phosphamide to avoid progressive, irre- shock-like feelings down the arms respiratory tract or gastrointestinal ill- versible organ damage. It is therefore and legs on neck flexion) ness a week or two before the weakness. important to try to confirm the diagnosis a sensory level Sensory symptoms and signs are not as quickly as possible, preferably with a dissociated sensory loss required for the diagnosis as a pure demonstration of vasculitis on biopsy of (ieproprioceptive loss ipsilateral to motor variant is well recognised. Some affected tissue.

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Table 1. Summary of the typical presentation of different causes of rapidly progressive weakness according to reflex changes. (The list of differential diagnoses is not exhaustive but should act as a guide when assessing such patients.)

Reflex changes Brisk reflexes Normal reflexes Patchy reflex changes Absent reflexes

Associated symptoms Bilateral upgoing Proximal Fatiguable ptosis Mononeuritis Facial weakness* Sensory signs Ptosis and signs plantars weakness Diplopia multiplex Distal sensory loss* (eg level) Diplopia Sensory signs No sensory Dysarthria Pain Back pain* Urinary retention Blurred vision* (eg level) changes Dysphagia Erosive Autonomic Urinary retention Rash* Proximal muscle arthopathy* disturbances Myalgia* weakness Vasculitic skin lesions* Renal failure* Differential diagnosis Spinal cord Inflammatory Myasthenia gravis Vasculitis Guillain-Barré Spinal cord Botulism pathology myositis syndrome pathology Lambert-Eaton Drug-induced myasthenic myositis syndrome Metabolic Guillain-Barré myopathy syndrome Viral myositis Investigations MRI Creatine kinase Serum anti- Serum Lumbar puncture MRI Nerve conduction Lumbar puncture Serum acetylcholine inflammatory Nerve conduction Lumbar puncture studies biochemistry receptor antibody markers studies Anti-voltage Muscle biopsy titre Auto antibody gated calcium Neurophysiology titres channel Tensilon test Nerve/skin/renal antibodies biopsy

* variable. MRI = magnetic resonance imaging.

Neuromuscular junction should be carefully monitored in an requiring respirator y support can be disorders acutely deteriorating myasthenic. If the started on this dose, but steroids should patient coughs, chokes or has a bubbly be introduced cautiously in those with Myasthenia gravis voice after swallowing a teaspoon of water, generalised disease not requiring inten- Myasthenia gravis is by far the most a nasogastric tube should be inserted. sive care because they can precipitate an common neuromuscular junction dis- Rapidly deteriorating respiratory func- acute deterioration in symptoms. order; it is most likely to present acutely as tion, as assessed by increasing respiratory Myasthenia is often misdiagnos ed, a ‘myasthenic crisis’ – rapidly progressive rate and falling FVC, is a sign of particularly in the elderly. Diagnostic weakness particularly affecting the bulbar impending intubation. Such patients will clues include both ptosis and weakness of and respiratory muscles. A cholinergic not be controlled with high-dose eye closure, clear fatiguability and vari- crisis from excessive doses of cholines- cholinesterase inhibitors. Neostigmine able signs when examined at different terase inhibitors is rare. Lambert-Eaton should be used with extreme caution times of day. It would be unusual to have myasthenic syndrome (LEMS) can present because of the high incidence of cholin- limb weakness without bulbar and/ or with respiratory failure, but this is an ergic side effects, and should never be ocular symptoms. Distal weakness is unusual manifestation of a rare condition. administered intravenously. recognised but rare. Extraocular muscle LEMS generally presents with subacute Short-term remission may be achieved weakness in myasthenia gravis can look proximal weakness (particularly of the by plasma exchange or IVIg, but steroids like nystagmus, giving the mistaken legs), absent reflexes and autonomic dys- are the mainstay of treatment, aiming for impression that the lesion is intracranial. function. Bulbar and respiratory function a dose of 1mg/kg/day. Patients already There is often a delay before the diag-

Inflammatory muscle disease Myasthenia gravis Drug-induced muscle disease Vasculitis Viral myositis Guillain-Barré syndrome Botulism

Hours Days Weeks Months

Fig 1. Time line giving approximate rate of onset of different conditions that can present with generalised weakness.

106 Clinical Medicine Vol 4No 2 March/April 2004 CME Neurology nosis can be confirmed by a positive titre Key Points of anti-acetylcholine receptor antibodies or detailed neurophysiological studies, so Respiratory failure is a common complication of acute neuromuscular disease and there is still a place for the Tensilon test high cervical cord lesions and should be monitored by measuring forced vital (edrophonium challenge test) in symp- capacity and respiratory rate tomatic patients. However, a mortality is associated with this test and it is open Urgent imaging is mandatory if there is any clinical suspicion of spinal cord disease tomisinterpr etation, so should be Treatment of Guillain-Barré syndrome with plasma exchange or intravenous performed only by an experienc ed immunoglobulin (IVIg) speeds up the rate of recovery clinician. Treatment of patients in a myasthenic crisis with plasma exchange or IVIg often results in significant short-term improvement Botulism Botulism should form part of the differen- A drug sideeffect or metabolic disturbance should be considered in a patient presenting acutely with proximal weakness, myalgia and high creatine kinase tial diagnosis of any individual presenting with rapidly progressing weakness, partic- KEY WORDS: Guillain-Barré syndrome, myasthenia gravis, spinal cord disease ularly if there is a history of IV drug abuse. Diagnostic clues are presence of autonomic symptoms and signs early in the cardiomyopathy and respiratory failure. may respond to immunomodulator y disease, such as sluggish pupil reactions Hypokalaemia, hypomagnesaemia and drugs. It is vital to remember that, what- and xerostomia, and weakness spreading hypophosphataemia can cause muscle ever the cause, progressive generalised from the ‘ top down’. Neurophysiological weakness, necrosis and even marked weakness will often affect respiratory and examination greatly assists in making the rhabdomyolysis. Conditions that predis- bulbar function. Such patients therefore diagnosis. By the time the diagnosis is pose towards such metabolic disturbances require close monitoring with respiratory appreciated, the window of opportunity include endocrinologi cal disturbances support if indicated. for administration of antiserum is usually such as a diabetic ketoacidosis, alcoholism long gone so treatment is supportive. If and excessive ingestion of potassium- wound botulism is suspected, a careful Acknowledgements losing compounds such as laxatives, search should be made for the focus of diuretics and liquorice. I am grateful to Ian Ormerod, Andrew infection and the wound debrided. Levy and Geraint Fuller for critical Drug-induced myopathy reading of the manuscript. Muscle disease In a patient presenting with progressive Acquired inflammatory muscle disease References proximal weakness and myalgia, consid- can present with rapid proximal weak- eration should always be given to 1Raphaël JC, Chevret S, Hughes RAC, ness, dysphagia and respiratory failure, drug-induced myopathy – particularly Annane D. Plasma exchange for Guillain- though in most cases the onset is more Barré syndrome (Cochrane Review). In: The relevant with the growing use of statins, insidious. Pain is a relatively uncommon Cochrane Library , Issue 2, 2002. Oxford: although many medications can cause feature, and the diagnostic pointers are Update Software. muscle damage. The combination of a 2Hughes RA, Raphaël JC, Swan A V, van marked proximal weakness with preser- statin with a fibrate is particularly risky. Doorn PA. Intravenous immunoglobulin vation of distal strength and reflexes (at A clinically significant statin myopathy is for Guillain-Barré syndrome (Cochrane least in the early stages) and sparing of Review). In: The Cochrane Library , Issue 3, generally accompanied by a significant the ocular muscles. Creatine kinase (CK) 2003. Oxford: Update Software. elevation in CK levels. If unrecognised, it levels are often grossly elevated. The 3Hughes RA, van der Meché FG. can progress to renal failure, and deaths Corticosteroids for Guillain-Barré syn- muscle biopsy may be diagnostic, though have been reported. 4 There will usually drome (Cochrane Review). In: The it may be normal even in classical cases be recovery of the muscle if the offending Cochrane Library , Issue 3, 2003. Oxford: because of the patchy nature of the Update Software. drug is stopped. disease. 4Sieb JP, Gillessen T. Iatrogenic and toxic myopathies. Review. Muscle Nerve 2003; 27:142–56. Viral myositis Summary Viral myositis can present with rapidly The key step when evaluating a patient progressive weakness and may be con- with progressive weakness is to establish if fused with GBS. Muscles are often tender the pathology is above or below the ante- and the CK elevated. The condition is rior horn cell. Lesions above require generally benign and self-limiting, urgent imaging; more distal pathologies though Coxsackie infection can cause a often have an inflammatory basis and

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