chapter 36 Neurology
INTRODUCTION AND OVERVIEW
This chapter discusses the more common neurological symptoms and disorders encountered in general practice, and some of the less-common classic neurological problems that are rarely seen in general practice. It is far from comprehensive—more detailed information can be found in textbooks of neurology.1,2
HEADACHE
Headache is probably one of the most common reasons for a patient to consult a general practitioner (GP). Many patients are fearful that they may have a serious neurological disorder, such as a brain tumour, whereas in reality this is rare. In primary care, the risk of brain tumour with a headache presentation is less than 0.1%.3 The most common causes of headache seen by a GP are primary headaches such as those associated with fever, tension headache and, less often, migraine. The challenge for the GP is to identify the very rare but more sinister causes of headache, such as subarachnoid haemorrhage (SAH), brain tumour, cranial arteritis, meningitis and so on. There are some clinical features that should increase the suspicion of a secondary cause for headache, such as:
MANAGEMENT
Headache of sudden onset
Tension headache and chronic daily headache
This is the most common type of headache encountered by the GP. The headache can be generalised, or focal, unilateral or bilateral. Focal neurological symptoms, nausea and systemic symptoms are absent. The headache typically commences some time after awakening and lasts most of the day, and fluctuation in severity during the day is characteristic. The patient may retire with the headache but usually awakens in the morning free of headache. Chronic daily headache is by definition the presence of headaches on a daily basis for six or more months. Although worsening of daily headache is regarded as a ‘red flag’ for a possible more sinister secondary cause of headache, in fact worsening in terms of increased duration and intensity of headache is not uncommon in these patients, particularly in the setting of increased use of analgesics, a syndrome referred to as the ‘analgesic overuse syndrome’. This is a vicious cycle, where increasing use of analgesics (even aspirin or paracetamol) leads to increasing severe headaches, leading to the use of even more of analgesia. A clue is that the patient often states: ‘I am taking all these pain killers and they do not seem to work any more.’ Many patients also have neck discomfort and when examined may have tenderness in the trapezius and sternocleidomastoid muscles; this often leads to a diagnosis of cervicogenic headache. Here the headache is assumed to be arising from disease in the cervical spine, and yet most patients do not have any demonstrable pathology on imaging or have osteoarthritis that may be an incidental finding, particularly in older patients where it is often present and asymptomatic. Relief of headache can be seen after massage to the neck muscles, physiotherapy or chiropractic, but the benefit may be short-term only.
A multifaceted approach to the treatment of tension-type headache, employing psychological, physiological and pharmacological therapies is recommended.4 The treatment for the analgesic overuse syndrome is for the patient to withdraw analgesia, which they often find difficult. The use of a tricyclic antidepressant for a short period has been shown to be beneficial.5
Migraine
Migraine is a complex headache disorder that has many manifestations. The aetiology is unknown. Patients experience recurrent headaches occasionally associated with recognisable precipitating factors. The diagnosis is entirely dependent on the history of the headache and associated features if present, as currently there are no tests to confirm the diagnosis. The patient with ‘classic migraine’ rarely presents a diagnostic problem. The headache is preceded by visual phenomena or neurological symptoms, referred to as the aura, that commence in one part of the body or visual field and spread, over a period of minutes (on average lasting approximately 30 minutes). The headache is usually throbbing in nature, and commences after the onset of the aura and increases in severity over minutes to hours. It is almost invariably associated with nausea, vomiting, photophobia and phonophobia. The headache persists for hours to days. The associated visual symptoms can vary from photopsia (positive phenomena such as flashing lights or bright dots) to patches of loss of vision, referred to as scotomata, that may or may not be surrounded by positive visual phenomena or fortification spectra. The diagnosis is more difficult in patients with recurrent headaches in which gastrointestinal, visual and neurological symptoms are absent. The diagnosis of probable migraine can be made if the patient experiences recurrent headaches that persist for hours on end and are either present on awakening or awaken the patient from their sleep. Rare forms of migraine include hemiplegic migraine and basilar artery migraine. Some patients can experience the aura of a migraine without the subsequent development of a headache, referred to ‘migraine without headache’ or ‘migraine equivalents’. Migraine headaches that occur only at the time of menstruation are referred to as ‘menstrual migraine’ and are due to the drop in the oestradiol level just prior to menstruation (see ch 52, Gynaecology).
Initial standard medical treatment often consists of simple analgesia, including non-steroidal anti-inflammatory drugs (NSAIDs) with an antiemetic drug such as prochlorperazine or metoclopramide. Ergot preparations, oral, rectal and subcutaneous, or the triptans, have all been shown to be effective.6,7
INTEGRATIVE MANAGEMENT OF HEADACHE/MIGRAINE
Prevention
Herbs and supplements
Magnesium
Intracellular magnesium levels are often lower in people with migraine headaches and magnesium deficiency is common. Two randomised controlled trials (RCTs)8,9 found that high-dose magnesium reduced the frequency and duration of migraine headaches. Magnesium can also help prevent migraine in women with cyclic headaches related to periods, and is also used in treatment of conditions involving muscle spasm or tension, fibromyalgia, anxiety states and tension headaches.
Riboflavin (vitamin B2)
Regular riboflavin may help reduce the frequency and shorten the duration of migraine headaches through anti-nociceptive and anti-inflammatory effects.10 Dose: 400 mg/day for at least 3 months, to assess effect in combination with feverfew and magnesium.
Feverfew (Tanacetum parthenium)
A systematic review of six RCTs11 concluded that evidence favours feverfew as an effective preventative treatment against migraine, and that it is well tolerated. Note that there is significant variation in the amount of active ingredient in commercially available feverfew preparations.
Physical therapies
Chiropractic
In one study12 including 127 people with migraine headaches, 22% of those who received chiropractic manipulation reported more than a 90% reduction of migraines and 49% reported a significant reduction of the intensity of each episode. There is some evidence to suggest that patients with tension headache and headache related to neck pain will benefit from chiropractic, although overall the evidence is less strong that chiropractic is beneficial for migraine.13
Physiotherapy
A review article14 evaluating nine studies that tested spinal manipulative therapy for tension or migraine headaches concluded that this technique is comparable to medications used to try to prevent either of these two types of headaches.
Acupuncture
Acupuncture is well studied as an effective treatment for various types of headache. Results from a study published in 200315 suggest that having an acupuncture treatment when migraine symptoms first begin is as effective as sumatriptan. Later in the course of the migraine attack, however, the medication works better than acupuncture. A 2001 Cochrane review16 found 26 trials on acupuncture for headaches. Of these, 16 trials investigated migraine headaches, six tension-type headaches and four various headaches. The majority, although not all, showed acupuncture to be better than placebo/sham acupuncture for tension/migraine headaches, although the quality of many trials was suboptimal. A more recent literature review by Endres and colleagues17 discussed 10 trials of acupuncture for migraine and concluded that a 6-week course of acupuncture was at least not inferior to a 6-month course of prophylactic treatments, and had a role in the integrated management of migraine headaches.
Drugs for prevention
Cranial arteritis
Cranial arteritis should be suspected in older patients, typically 75 years of age and older—it is rarely seen in patients under the age of 50 years. The headache is of insidious onset of days to weeks, often with systemic ill health, fever, polymyalgia rheumatica, scalp tenderness and jaw claudication, with the latter two virtually pathognomonic. The ESR is raised, often as high as 100, but may be normal early in the course of the illness, and therefore the ESR should be repeated once or twice per week when the diagnosis is suspected and the initial ESR is not raised. Occasionally the diagnosis can be made at the bedside by detecting thrombosed temporal arteries (see Fig 36.1). If the clinical suspicion is high and despite a normal ESR, the patient should be treated with high-dose corticosteroids and a temporal artery biopsy obtained as a matter of urgency. Delays in treatment can result in blindness and, less frequently, cerebral infarction.
FUNNY TURNS
INVESTIGATIONS
The investigations already alluded to rarely, if ever, establish a diagnosis in patients with intermittent disturbances of function. If seizures are frequent or can be precipitated by sleep deprivation or hyperventilation, then video-electroencephalographic monitoring may occasionally detect a seizure (see Fig 36.2). Holter monitoring can on rare occasions detect complete heart block in patients with suspected Stokes-Adams attacks. Symptoms related to hyponatraemia, hypokalaemia or hypocalcaemia are so rare that routine electrolyte estimation is rarely helpful. A full blood examination could detect anaemia or evidence of an infection, but intermittent symptoms related to either of these entities are very rare. Imaging such as CT scan or MRI scan is usually normal, except for patients with focal seizures.
MANAGEMENT
Epilepsy
Tonic-clonic seizure
Tonic-clonic seizure may or may not be preceded by an aura. An aura suggests a focal onset. The patient stiffens and may ‘cry out’—the so-called ‘cri de chat’—the eyes remain open, and this tonic phase, lasting up to 30 seconds, is followed by the clonic phase, with repeated flexing movements of all four limbs. Tongue or cheek biting and incontinence of urine and faeces may also occur. There is a period of post-ictal drowsiness and confusion. Most episodes last less than 2–3 minutes, rarely as long as 20 minutes.19
Diagnosis
The diagnosis is essentially a clinical one and based almost entirely on the history of the episode, as only rarely do patients have a seizure while undergoing electro-encephalography (EEG). Current recommendations advocate an EEG, CT or MRI brain scan in all patients presenting with a first unprovoked seizure. The presence of epileptic discharges on an EEG in patients with their first seizure increases the risk of recurrence. Many patients presenting with their first apparent seizure have, on detailed questioning, had unrecognised seizures in the past.20
Treatment of seizures and epilepsy
Most seizures last only a matter of 1–2, rarely 5, minutes, and the initial management is simply to prevent the patient from harming themselves and to lie them on their side when the seizure is finished. Prolonged seizures and status epilepsy require prompt intervention. Intravenous (IV) lorazepam is the drug of choice in both adults and children.21
Carbamazepine is the drug of choice for partial or focal seizures, and valproic acid for generalised seizures.22 However, carbamazepine interferes with the oral contraceptive pill and causes drowsiness; valproic acid can result in hair loss and obesity, side effects that young women are often not willing to contemplate. There are many guidelines23 and these are frequently evolving and should be consulted on a regular basis.
Integrative management of epilepsy
The adverse effects of antiepileptic pharmaceuticals make it difficult to attain optimal dosage levels in order to prevent seizures in many cases.24 Current evidence suggests that 25–50% of individuals with epilepsy have tried some form of CAM therapy.25–27 It is important to note that these therapies are not a substitute for medication; however, depending on the effectiveness of the intervention(s), dosage reductions under medical supervision may be possible.28
Mind–body medicine
A systematic review assessing several different meditative practices (meditation, meditative prayer, yoga, relaxation) has revealed some evidence for the efficacy of meditation in the treatment of epilepsy.29 In particular, studies have demonstrated that transcendental meditation (TM) may be a potential antiepileptic treatment. However, further trials are required, as many of the EEG recordings during TM (increased alpha, theta, gamma frequencies with increased coherence and synchrony) are similar to the neuronal activity that occurs during seizures.30
Sleep
It has long been known that there is a close relationship between the physiological state of sleep and the pathological process underlying epileptic seizures, but the connection is still not well understood.31 Sufferers of epilepsy often demonstrate multiple sleep abnormalities, such as increased sleep latency, fragmented sleep, increased awakenings and stage shifts and an increase in stages 1 and 2 of non-REM sleep.32 It is important that any sleep disorders are identified and managed as soon as possible, as sleep deprivation has been shown to increase the frequency of epileptiform discharges and seizures.33–35 Sleep quality, as well as daytime alertness and neurocognitive function, can be improved by anticonvulsant medications, ketogenic dietary principles and vagus nerve stimulation.33 However, it should be noted that poor sleep can also be an adverse effect of some anticonvulsant drugs.24,36
Sunshine
Individuals with epilepsy who have been on long-term treatment with various anticonvulsants may develop hypocalcaemia, osteomalacia and osteopenia that is independent of vitamin D metabolism. It has been demonstrated that there are regional variances in the incidence of drug-induced bone disease and this has been attributed to variances in sunlight exposure, with the majority of reports coming from areas of low sunshine or from institutionalised patients.37,38
Exercise
In times past, exercise was restricted for those with epilepsy, rather than encouraged, as it is today. As many people with epilepsy still fear suffering an exercise-induced seizure, they often lead a sedentary life and have poor physical fitness.39 Although there have been rare cases of exercise-induced seizures, both clinical and experimental data have shown that exercise can reduce the frequency of seizures as well as improving cardiovascular and psychological health.40,41 Indeed, current evidence demonstrates that regular exercise may have a moderate seizure-preventative effect in 30–40% of this population.39 Most sporting activities, including contact sports, are safe to participate in, according to current medical recommendations. Supervised water sports and swimming are also considered safe, provided seizures are well controlled. However, sports such as hang-gliding and scuba diving are not recommended, as there is a high risk of severe injury or death if a seizure were to occur.40 It is imperative that medical advice regarding exercise is individualised for each patient, taking into account their seizure type and frequency.40
Yoga
Recent studies have shown that yoga can reduce seizure index and increase quality of life in people with epilepsy.42 Yoga has also been shown to significantly improve parasympathetic parameters, suggesting that it may have a role in the treatment of autonomic dysfunction in patients with refractory epilepsy.43
Diet
Maintaining good blood sugar balance, identifying and eliminating allergenic foods and avoiding suspected triggers such as alcohol, artificial sweeteners, diet soft-drinks, energy drinks and MSG are important in the management of epilepsy.28,44,45 Growth retardation is common among children with epilepsy and this appears to be secondary to poor dietary intake. Dietary intake of vitamins D, E and K, folate, calcium, linoleic acid and alpha-linolenic acid has been found to be below the recommended daily allowance (RDA) in approximately 30% of children with intractable epilepsy.46
Studies of dietary treatments for epilepsy suggest that approximately 50% of children have a 50% reduction in seizures after 6 months. Approximately one-third will achieve more than 90% reduction in their seizures. Such diets maintain their efficacy when provided continuously for several years. Furthermore, long-term benefits may be seen even when the diet is ceased after only a few months, indicating neuroprotective effects.47 Other dietary guidelines for the management of epilepsy are given below. Recommending such diets in the management of epilepsy needs to be balanced with the overall nutritional needs and health of the patient.
Ketogenic diet
The ketogenic diet is a high-fat, low-carbohydrate, high-protein diet used to treat medically refractory epilepsy.48 At least 15–20% of patients on the ketogenic diet experience more than 50% reduction in seizure frequency. For this reason, the ketogenic diet should be considered an early treatment for drug-resistant epilepsy, not a ‘last resort’.49–51 The ketogenic diet may also be a valuable therapeutic option for children with drug-resistant focal epilepsy, particularly those with recent deterioration of seizure control.52,53
Modified Atkins diet
The modified Atkins diet is a less-restrictive ketogenic diet. It has no restrictions on calories, fluids or protein, and does not involve fasting. As for the ketogenic diet, high-fat foods are encouraged, with 10 g/day of carbohydrate allowed in children and 15 g/day in adults. Approximately 45% of patients have 50–90% seizure reduction, with 28% having more than 90% seizure reduction.54 The ketogenic diet appears to exert its effects more quickly, although by 6 months the difference is no longer considered significant.50
Low glycaemic index diet
A study in 2009 reported on the efficacy, safety and tolerability of the low glycaemic index diet in paediatric intractable epilepsy. More than 50% reduction from baseline seizure frequency was seen in 42%, 50%, 54%, 64% and 66% children at 1, 3, 6, 9 and 12 months respectively.55
Polyunsaturated fatty acids
Increased concentrations of both ketone bodies and polyunsaturated fatty acids (PUFAs) have been found in the cerebrospinal fluid and plasma of patients on the ketogenic diet, and it is thought that a high dietary intake of PUFAs may be one mechanism responsible for the potent anticonvulsant effects of the ketogenic diet.56,57 Supplementation with omega-3 fatty acids has also been shown to prevent status epilepticus-associated neuropathological changes in animal studies.58 Although PUFAs have been shown to reduce seizures in several animal models, available data regarding the effects of supplementation in epileptic patients (1–3 g EPA/DHA daily) reveal mixed results with respect to seizure frequency.59–61 More research is therefore required before PUFAs can be definitively recommended as a treatment option for epilepsy.56
Amino acids
Current research suggests that serotonin has an antiepileptic effect, and serotonin receptors are expressed in almost all networks involved in epilepsies. Some SSRIs, such as fluoxetine, have been found to improve seizure control, and some antiepileptic drugs have recently been found to increase endogenous serotonin levels.62–64
Tryptophan
Tryptophan is an essential amino acid and the only brain precursor of serotonin. It has been estimated that patients with epilepsy have approximately 30% lower brain intake of tryptophan compared with controls. Whey proteins that are high in tryptophan but lower in other large neutral amino acids are currently being trialled in combination with antiepileptic medications.62
Taurine
Taurine is one of the most abundant free amino acids found mainly in excitable tissues. Taurine is necessary for the production of GABA, one of the major inhibitory neurotransmitters in the limbic system.65 For this reason, drugs that target GABA receptors are the mainstay of treatment of seizures, with the recent transplantation of GABA-producing cells effectively reducing seizures in several well-established models.66,67
There have been multiple animal studies demonstrating that taurine-fed animals have increased levels of GABA and a higher threshold for seizure onset compared to controls.65 Furthermore, increased taurine levels in the hippocampus improve membrane stabilisation, significantly reducing neuronal cell death and favouring recovery after neuronal hyperactivity.68,69
Carnosine
Carnosine is an amino acid with many of the features of a neurotransmitter. It has the ability to act as both a neuromodulator and a neuroprotective agent, and it may indirectly influence neuronal excitability by modulating the effects of zinc and copper.70–72 Carnosine may have a significant anticonvulsant effect and, as such, it may prove to be a potential anticonvulsant treatment for epilepsy in the future.73
Antioxidants
Excessive production of free radicals with neuronal hyperexcitability have been strongly implicated in the pathogenesis of idiopathic epilepsy. There is therefore a possible role of antioxidants in combination with antiepileptic drugs for better seizure control,74–76 although, as with other chronic illnesses, it is likely that a nutritious diet rich in antioxidants such as vitamins A, C and E is likely to be far more effective than a poor diet supplemented by antioxidants. Results have thus far been mixed for vitamin E supplementation, and more studies are required before definitive recommendations can be made.77
Selenium deficiency has been implicated in the pathogenesis of epilepsy.78 Anticonvulsants may further deplete total body selenium stores, and failure to advise appropriate selenium supplementation, especially to pregnant women taking sodium valproate, may increase the risk of neural tube defects or other free radical mediated damage.79
Zinc
Altered zinc homeostasis appears to be associated with epilepsy; however, the definitive role of zinc as a neuromodulator in synapses is still uncertain.80,81
Other vitamins and minerals
Many anticonvulsant medications are known to reduce folic acid levels, subsequently raising homocysteine levels. Homocysteine, however, is known to be a convulsing agent that can result in increased seizure recurrence and intractability to medications. In addition, anticonvulsant medications can disturb lipid metabolism, creating hypercholesterolaemia, dyslipidaemia and altered uric acid metabolism. As such, routine supplementation with folic acid, vitamin B12, B6, C, E and beta-carotene for all those on anticonvulsant medications is important.82
A Cochrane review has found that vitamin B1 improves both neuropsychological and cognitive functions in patients with epilepsy. In the same review, vitamin D was also found to improve bone mineral density in those taking anticonvulsant medications.28,77
Manganese deficiency has also been associated with seizures in both animals and humans, according to a systematic review. More research is needed, as it is currently unclear as to whether this is a cause or an effect of the convulsions.83
Herbs
Herbal medicine has been used for centuries in many cultures for the treatment of epilepsy and some patients may be self-medicating with herbal medicines. It is therefore important for the GP to ask about the patient’s use of herbal preparations, as many herbs can increase the risk of seizures by affecting cytochrome-P450 enzymes and P-glycoproteins, or through possible contamination by heavy metals.84,85
Well-designed clinical trials of herbal therapies for epilepsy are scarce. However, based on animal studies and numerous anecdotal observations of clinical benefits in humans, further research is certainly warranted.84,85
The flavonoid derivatives from Scutellaria baicalensis Georgi, Artemesia herba-alba, Melissa officinalis and Salvia triloba have all been found to exert anticonvulsant effects by exhibiting significant affinity for the GABA(A) receptor benzodiazepine binding site.86,87 Ginkgo biloba appears to have the capacity to both induce and inhibit seizures.88
Interestingly, Curcumin has also recently been shown to significantly prevent generalisation of electroclinical seizure activity as well as the pathogenesis of iron-induced epileptogenesis.89,90 Further studies are required.
Various Chinese herbs, such as Chaihu-longu-muli-tang, appear to have antiepileptic properties, and it also appears that the reduction in seizure frequency may be related to the antioxidant effects of the herbs.91 Shitei-To is another TCM formulation that may have therapeutic effects in the prevention of secondarily generalised seizures. It is made from three medicinal herbs: Shitei (calyx of Diospyros kaki L.f), Shokyu (rhizome of Zingiber officinale Roscoe) and Choji (flower bud of Syzygium aromaticum).92
Prevention
Lifestyle measures that may be important in the management of epilepsy have been discussed previously. Furthermore, living as ‘cleanly’ as possible is important for individuals with epilepsy, as there are numerous documented toxic causes of seizures. These include substance abuse (alcohol and recreational drugs), exposure to various industrial and household products, occupational nickel and other heavy metals.94 Animal studies have demonstrated that blood lead levels similar to those found in humans living in urban areas with high pollution levels can lower seizure threshold.95
Research on hospital admissions of patients in status epilepticus reveals several environmental factors that are either protective or precipitative. It appears that there is a significant diurnal pattern, with the majority of admissions occurring between 4 pm and 5 pm, and least admissions in the early morning hours. Admissions also vary significantly throughout the lunar cycle, with the peak at day 3 after the new moon and trough at 3 days before the new moon. Admissions have been noted to be highest on bright, sunny days, whereas dark days, high humidity and high temperature appear to be significantly protective factors.96
MOTOR WEAKNESS
EXAMINATION
Central nervous system (CNS) causes of weakness produce a classic ‘upper motor neuron’ pattern of weakness with finger extension, shoulder abduction and elbow extension in the upper limbs and hip flexion, weakness of dorsiflexion of the feet and knee flexion in the lower limbs. This pattern of weakness would most often be associated with increased tone (with or without clonus), increased reflexes and up-going plantar responses. If the facial muscles are affected with CNS, then the forehead is not affected. In disorders of the peripheral nervous system (PNS), the pattern of weakness will indicate whether the problem is in the anterior horn cell (usually associated with significant wasting and fasciculations), motor nerve root (usually associated with significant radicular pain), plexus, peripheral nerve, neuromuscular junction (fluctuating weakness with exercise) or muscle. The presence of sensory signs excludes disorders of the anterior horn cell, motor nerve root, neuromuscular junction or muscle. In disorders of the PNS, the tone may be normal or decreased, the reflexes are often absent, plantar responses are down-going and, if present, sensory signs will reflect the site of the problem in the PNS. Disorders of muscle are usually associated with preserved reflexes (rare exceptions to this include myotonic dystrophy and inclusion body myositis). If the weakness affects the face, it is important to see whether the muscles that wrinkle the forehead (frontalis muscle) are affected; if so, this points to a lower motor neuron facial palsy. If the forehead is not affected but there is weakness around the mouth, this is an upper motor neuron facial weakness.
MANAGEMENT
Management is disease specific and is discussed below.
Facial weakness
Bell’s palsy
Corticosteroids and aciclovir have been recommended in the belief that functional outcome is improved.97 However, a 2009 Cochrane review concluded that corticosteroids and aciclovir have not been proved to be beneficial.98 Subsequent to this review, a large randomised controlled trial99 demonstrated complete recovery at 3 months in 83% of patients treated with prednisolone (50 mg per day for 10 days), as opposed to 63.6% for patients treated with placebo. At 9 months, 94.4% of the prednisolone-treated group had completely resolved, compared to 81.6% for the placebo. No benefit was found from aciclovir.
Acute and chronic inflammatory demyelinating neuropathy
The term acute inflammatory demyelinating neuropathy (AIDP) has replaced the term (Landry) Guillain-Barré (Strohl) syndrome. This presents with the rapid onset of weakness usually affecting the limbs, with proximal weakness in the lower limbs and distal weakness in the upper limbs initially, subsequently becoming generalised weakness of the limbs. There is almost invariably neck flexion and occasionally neck extension weakness. The cranial nerves may also be affected, resulting in bilateral facial weakness, palatal weakness or weakness of the extra ocular muscles, resulting in variable patterns including a pseudo-internuclear ophthalmoplegia (INO). The reflexes are absent and there may or may not be peripheral sensory loss. Some patients develop involvement of the autonomic nervous system, resulting in arrythmias, periods of hypertension and hypotension and disturbances of bladder and bowel function. The respiratory muscles are involved in severe cases, and patients will often require long-term ventilation. In addition to supportive measures, either intravenous immunoglobulin (IVIG) or plasma exchange is used in the acute phase.100–102 IVIG is probably the treatment modality of choice, for ease of use. The prognosis is variable, with approximately 75% of patients making an excellent recovery; the remainder have mild or moderate impairment, with severe disability occurring in less than 5% of patients.
Chronic inflammatory demyelinating neuropathy (CIDP) can cause the same patterns of weakness as AIDP but evolves more slowly (by definition over more than 6 weeks). IVIG or corticosteroids should be considered in sensory and motor CIDP. IVIG should be considered as the initial treatment in pure motor CIDP.103
Motor neuron disease
Motor neuron disease (MND), also referred to as amyotrophic lateral sclerosis (ALS), presents with weakness and fatigue associated with significant muscle wasting and fasciculations in the absence of any sensory symptoms. Muscle cramps can occur. Four distinct clinical phenotypes have been identified, with different rates of progression and survival. Patients presenting with global involvement have the worst prognosis, while patients presenting with a flail arm survive longer.104 When MND affects the bulbar musculature, patients present with a characteristic dysarthria, with wasting and fasciculations of the tongue. At present there is no specific treatment, but these patients should be cared for in specialised centres with expertise in MND.
Myasthenia gravis
Myasthenia gravis is a very rare autoimmune disease and most GPs are not likely to see a case. The characteristic feature is a weakness that is exacerbated by use of the muscle and reduced in intensity by rest. Myasthenia gravis can remain confined to the extra ocular muscles, where it presents with intermittent ptosis and variable horizontal and vertical diplopia—for example, when reading or watching television. Myasthenia affecting muscles in the rest of the body is referred to as generalised myasthenia. Myasthenia affecting the bulbar musculature (the lower four cranial nerves) will present with dysarthria exacerbated by talking, dysphagia and difficulty chewing, exacerbated by eating. When it affects the muscles of the arms and legs, patients will complain of increasing weakness when they are trying to do activities such as hanging the washing on the line or washing their hair, or they may complain of increased difficulty walking, and of having to rest. The diagnosis can be made at the bedside by asking the patient to repeatedly exercise and by demonstrating increased weakness; or, if it affects the extra ocular muscles, by asking the patient to look up, and observing increased ptosis and the development of increasing diplopia, the longer the patient is looking up. Applying ice to the ptosed eyelid can lead to a dramatic resolution of the ptosis.105 Another bedside test is the Tensilon test, where edrophonium hydrochloride is injected and a transient improvement or resolution of symptoms can be observed. The ice test and the Tensilon test both have a high sensitivity (92–95%) and specificity (97%). Antibodies directed against the acetylcholine receptor (ACHR) are highly specific (98%) but the sensitivity varies from one report to another, from as low as 54% to as high as 88%.106 Electrodiagnostic studies include repetitive nerve stimulation, where a decremental response is observed and the variability of stimulation of the acetylcholine receptor by acetylcholine can be observed with single fibre electromyography (SFEMG)—this is referred to as increased jitter. All patients with myasthenia gravis should have a CT scan of the chest to look for thymic hyperplasia (usually seen in younger patients) or a thymoma (in older patients); these can be either benign or locally malignant. Ocular myasthenia gravis sometimes responds to the cholinesterase inhibitor pyridostigmine.107 Thymectomy is recommended for patients with thymic hyperplasia108 or thymoma.109 IVIG is very effective in the treatment of myasthenic crisis and can be used preoperatively prior to thymectomy or prior to any surgery in patients with generalised myasthenia gravis.101 Corticosteroids, other immunosuppressive agents and plasma exchange are used in patients who fail to respond to thymectomy.110,111
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