Recurrent vertigo is almost never due to a serious neurological problem – it is almost always due to one of three basically aural conditions: benign positional vertigo, Meniere’s disease or migraine. In Balance Disorders Clinic at Royal Prince Alfred Hospital, Sydney, about 150 new patients are seen each month; about 100 with recurrent vertigo and 50 with chronic or subacute loss of balance. Of the 100 or so patient with recurrent vertigo maybe one will have a neurological cause such as transient ischaemia or episodic ataxia, apart from migraine. Of the 50 patients with imbalance only about 10 will have a peripheral vestibular cause, i.e. unilateral or bilateral vestibular loss causing chronic vestibular insufficiency or benign positional vertigo (BPV) which causes imbalance and falls in the elderly. Of the other 40 only about half will have a single or principal identifiable neurological cause for the imbalance such as sensory neuropathy, hydrocephalus, spinal cord disorder; the other half, all elderly, will have several potential contributing factors such as poor vision, joint replacement, arthritis, maybe presbystasis.
In contrast a first ever attack of acute spontaneous vertigo, like a first ever headache, backache or loss of consciousness is due to serious problem until proven otherwise. While viral neurolabyrinthitis is the single most frequent cause of isolated acute spontaneous vertigo, the most important differential diagnosis is acute cerebellar infarction, a potentially lethal condition.
In general the 7 most common mistakes made by neurologists in evaluating dizzy patients are:
1. Not distinguishing vertigo from imbalance;
2. Not doing or not knowing how to do a positional test;
3. Not doing or not knowing how to do a head impulse test;
4. Not realizing that migraine is a frequent cause of vertigo without headache;
5. Not ordering or not being able to interpret an audiogram;
6. Not arranging to review the patient during a vertigo attack;
7. Ordering a magnetic resonance imaging (MRI) instead of examining the patient properly.
WHAT IS VERTIGO ?
a. Vertigo is an illusion of rotation. It is due to unequal neural activity between the left and right vestibular nuclei. Unequal activity can be produced spinning a normal person at constant speed for about 20 seconds and then suddenly stopping them, by heating or cooling one labyrinth as happens in the caloric test, or by moving otoconial particles along semicircular canal duct as happens in benign paroxysmal positional vertigo. It can also be produced by sudden unilateral destruction of a normal vestibular end-organ, nerve or nucleus or vestibulo-cerebellum, a structure that normally inhibits the ipsilateral vestibular nucleus. In contrast bilateral simultaneous vestibular destruction produces imbalance but not vertigo; in fact a patient with bilateral vestibular loss will never again experience vertigo, as would a normal subject, from unilateral vestibular stimulation.
b. Vertigo is always temporary. Even after the vestibular nerve on one side has been surgically severed, the vertigo and nystagmus that invariably follow will always abate within a few days. This is not because the vestibular nerve has rejoined but because neurochemical changes have taken place in the brainstem during the process of vestibular compensation which restores symmetrical vestibular nucleus resting neural activity 29.
c. Vertigo is always made worse by head movement so that patients who are dizzy all the time and are happy to move around when they are dizzy do not have vertigo.
Patients with aural vertigo should not lose consciousness but some patients can’t give a convincing answer even to simple questions such as: "Did it feel like you were losing balance or like you were losing consciousness?” or “Did you feel like you were going to pass out or fall over?" Patients with vertigo might lose consciousness if they have been vomiting a lot, or if they had an otolithic drop attack 76,77 and sustained a head injury on the way down.
Witness descriptions can be helpful in identifying other paroxysmal disorders such as seizure and syncope but are not in identifying vertigo. Panic attacks with hyperventilation, can cause dizziness, not vertigo, and patients with vertigo attacks can develop panic attacks and agoraphobia 78. "Phobic postural vertigo" is a variant of this problem in which patients, often with obsessive-compulsive personalities, complain of a mild subjective disturbance of balance while standing or walking, with momentary illusions of motion 19. The symptoms usually occur in specific places or situations, and are associated with a distressing anxiety. Many cases follow a well-documented peripheral vestibulopathy. While not everyone likes the name "phobic postural vertigo"22, typically patients like this improve with support and explanation 85.
POSITIONAL VERTIGO
Benign paroxysmal positioning vertigo (BPPV) is the most common cause of recurrent vertigo 93,121. The history can be unmistakable: "… whenever I turn in bed at night, or I hang the washing on the line or look under my car I am dizzy.” In most patients the BPPV will occur in bouts lasting several weeks and will then spontaneously remit, only to return weeks, months, or even years later 26,131. Any patient with repeated bouts of vertigo over many years with no vestibular abnormalities on examination or testing is most likely has BPPV. BPPV is due to the movement of stray otoconial particles within the duct of one semicircular canal, usually the posterior and it is possible to remove these and so to put the patient into immediate remission basically by rolling the patient slowly by 180 degrees, from the most provocative position towards the normal side 43.
The Dix-Hallpike positioning test is the key to diagnosis 143. The aim of the positioning test is to make otoconia in the posterior semicircular canal move and so provoke vertigo and nystagmus. Brandt and Daroff 18 and then Semont et al 98 and Epley 34 showed that making the otoconia move within the duct allows them to be removed from the duct.
Consider a patient with left posterior semicircular canal BPPV, seated on a bed (Figure 1). In this position the posterior semicircular canal is gravitationally vertical so that its ampulla is its lowermost part; any otoconia in the duct will have come to rest next to the cupula (Fig. 1-start). The patient's head is now turned to the left and the patient is suddenly pitched backwards (in the plane of the posterior semicircular canal) until the head is hanging over the end of the bed so that the lowermost point becomes the midpoint of the posterior semicircular canal duct rather than the ampulla. The otoconia will now fall down from the cupula and come to rest at the midpoint of the duct. As they fall away from the cupula they create a negative fluid pressure and so pull on the cupula producing an ampullofugal deflection which is excitatory for primary afferents of the posterior semicircular canal. As a result there is not only a brief (~20 sec) paroxysm of vertigo, but also of a nystagmus with upbeating and counterclockwise fast phases, from the patient's point of view. That is, the rotation axis of the nystagmus is at 90 degrees to the plane of the stimulated semicircular canal, in this case the left posterior canal 8. If the patient is now slowly rotated by 180 degrees in towards his right, until the right side of his face is touching the bed, the posterior semicircular canal will have been inverted (Fig.1) so that the common crus, which joins the anterior and posterior semicircular canals, is now the lowermost point. At this stage the otoconia should move further along the semicircular canal duct and produce another, but this time less severe, paroxysm of vertigo and of counterclock-wise upbeating nystagmus. The patient, still face down, now stands up and the otoconia will continue along the common crus back into the vestibule. This is in essence the particle repositioning or perhaps better termed "liberatory" manoeuvre, as described by Epley. It will stop the BPPV attacks in about four out of five patients 143 although the condition usually remits by itself 75. Those who are resistant to repeated repositioning manoeuvres can be cured by surgical occlusion of the posterior semicircular canal 147. Post-traumatic cases in particular can be bilateral but it is sometimes difficult to tell bilateral BPPV from unilateral BPPV with a vigorous off direction (ampullopetal) nystagmus on turning toward the unaffected side134.
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Figure 1: The Epley type particle repositioning manoeuvre in a patient with left posterior canal BPPV. |
In most patients with BPPV there are no other symptoms and there is no demonstrable abnormality of vestibular or auditory function. In a few it follows acute vestibular neuritis or occurs during the course of a progressive inner ear disease such as Meniere's disease or Cogan's syndrome 86. Very rarely typical BPPV occurs in a patient who turns out to have a posterior fossa disease such as a multiple sclerosis 40, tumour 32,55, malformation, or degeneration 13 but BPPV is common enough for a patient to have both 39.
Lateral (or horizontal) semicircular canal BPPV is a variant in which the nystagmus is horizontal and usually beats toward the lowermost ear (geotropic) indicating that the otoconia in the duct are falling toward the cupula and sometimes beats toward the uppermost ear (ageotropic) indicating that the otoconia are attached to the cupula 37. Treatment of lateral semicircular canal BPPV consists of rotating the recumbent patient 360 degrees from the bad side towards the good side and then having the patient sleep only on the good side so that the otoconia can find their way out of the lateral semicircular canal back into the vestibule 117,142.
RECURRENT SPONTANEOUS VERTIGO
A patient with recurrent attacks of isolated spontaneous vertigo most likely has either Meniere's disease or migraine. The mechanism of Meniere's disease appears to be episodic endolymphatic hypertension and distension which produces attacks of spontaneous vertigo with a low frequency hearing loss, tinnitus, and a sense of fullness or blockage in the affected ear 47,109. The vertigo attacks usually last for a few hours, but the tinnitus and hearing loss might continue for days. The attacks might occur days, months, or even years apart. After the first few attacks of vertigo vestibular and cochlear function recover, so that the caloric test and the pure tone audiogram will both be normal. Later, after many more attacks of vertigo a permanent loss of auditory and of vestibular function becomes apparent even in between attacks. The key to the diagnosis is repeated audiometry to show a fluctuating loss frequency hearing loss (Fig 2). Improvement in hearing with glycerol or furosemide dehydration and transtympanic electrocochleography can help confirm the diagnosis 89. Meniere's disease can remit at any stage but if it does progress then in the late stages the patient is still subject to attacks of spontaneous vertigo but also has continual tinnitus in a deaf ear that distorts and recruits sound so that normal speech is unintelligible and loud sounds are painfully loud. Strict dietary sodium restriction aiming for a urinary sodium less than 50 mmol/day can be more effective and less troublesome than diuretics (http://oto.wustl.edu/men/sodium.htm).
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Figure 2: Serial audiograms in a patient with right Meniere’s disease showing a fluctuating low-frequency unilateral sensorineural hearing loss with full recruitment – note the normal acoustic reflexes at about 100dB. |
Endolymphatic sac decompression can stop the vertigo attacks but can't restore the hearing and should not destroy any auditory or vestibular function. Low-dose intratympanic gentamicin, unlike labyrinthectomy, will not only stop the vertigo but should preserve hearing 154, probably as well as intracranial vestibular nerve section 49.
A common clinical problem is the patient who presents with repeated attacks of spontaneous vertigo, but is unaware of any temporary deafness, tinnitus, or fullness in one ear at the time of a vertigo attack, and who has no clinical abnormalities, a normal audiogram, and a normal caloric test. Such a patient could still have Meniere's disease. The patient might have had a temporary low-frequency hearing loss during the vertigo attack but would not have noticed it as the loss was below 1.5 kHz, the centre of the speech spectrum, and particularly they are too busy being sick to worry about a little deafness in one ear. There are also patients who have repeated spontaneous vertigo attacks for many years before they develop a unilateral tinnitus and hearing loss and the diagnosis of Meniere's disease finally becomes obvious. But a patient with recurrent vertigo attacks and normal hearing might have vestibular migraine 125.
Some migraineurs will have vertigo as their aura 114, and will then develop a typical hemicranial headache with nausea and vomiting. Other migraineurs and their relatives will have repeated attacks of spontaneous vertigo, apart from the attacks of headache, typically lasting less than an hour, with nausea and even vomiting, but without any hearing disturbance or headache at the time 21. Attacks such as these have been called basilar migraine, although Bickerstaff was referring to a more dramatic clinical pattern 16. During attacks of migrainous vertigo there will be vestibular abnormalities that can look central, peripheral or both 145. Migrainous positional vertigo needs to be distinguished from benign positional vertigo due to vestibular lithiasis 144. Migraine can also cause a more chronic form of imbalance (41,150). Vertigo attacks in migraineurs can respond to medications used to treat migraine headaches such as an ergot, a triptan 115, or even aspirin and in some patients the vertigo attacks can be prevented by regular treatment with a beta-blocker, a calcium channel blocker, a tricyclic, valproate, acetazolamide, or methysergide 128.
DISEASES THAT DON’T USUALLY CAUSE RECURRENT VERTIGO
Certain diagnoses are almost certain to be wrong in a patient who has recurrent isolated vertigo attacks, a normal clinical examination and no objective loss of auditory or vestibular function. Acute otitis media does not cause vertigo unless there is a suppurative labyrinthitis. Chronic otitis media can, rarely, produce vertigo due secondary endolymphatic hydrops or cholesteatoma causing a perilymph fistula can but not without a hearing loss. Probably all cases attributed to spontaneous perilymph fistula are in fact a dehiscence of the superior semicircular canal into the middle cranial fossa 107 and not of the lateral semicircular canal into the middle ear. Superior canal dehiscence can also produce an air-bone gap on the audiogram that can, superficially at least, mimick otosclerosis 59,105,108. Acoustic neuroma, (vestibular schwannoma), unless intralabyrinthine, rarely produces attacks of spontaneous vertigo, and maybe never in a patient who has no fixed unilateral or asymmetric abnormalities of auditory or vestibular function 113. Microvascular loop compression is a validated cause of paroxysmal symptoms related to the trigeminal and facial nerves, but the evidence that microvascular compression of the vestibular nerve causes paroxysmal vestibular symptoms, or any symptoms at all, is unconvincing 11. The anterior inferior cerebellar artery (AICA) normally loops into the internal auditory canal and is not a bona fide cause of symptoms. Frequent brief attacks of vertigo accompanied by unilateral hyperacusis or tinnitus can respond to treatment with carbamazepine and have been called "vestibular paroxysmia" 20 there is scant evidence for symptomatic microvascular compression in these patients.
Fisher is still correct: transient posterior circulation ischaemia is unlikely to be correct in a patient who has recurrent attacks of isolated vertigo 38. Nonetheless it could be suspected in a patient in whom some of the vertigo attacks are accompanied by other symptoms of brainstem dysfunction such as diplopia 50,53,118. In the absence of any simultaneous brainstem symptoms, a short history, of days rather than months, of frequent brief vertigo attacks lasting minutes rather than hours several times a day, should raise the suspicion that the attacks are posterior circulation transient ischaemic attacks (TIA). Hearing symptoms, tinnitus and deafness if unilateral and occuring at the same time as the vertigo attacks suggest an aural rather than a brainstem problem. In contrast sudden, temporary bilateral hearing loss does suggest brainstem ischemia 97. Vestibular function tests are expected to be normal in patients with posterior circulation ischaemia and are only of help in a negative sense: if they show a definite unilateral abnormality this will suggest an aural rather than a central cause for the vertigo.
Rarely isolated vertigo attacks can be produced by stenosis or impending thrombosis of one vertebral artery or more seriously of the basilar artery; in such cases intervention, thrombolysis, angioplasty and stenting might be required, sooner rather than later. 122,157.
With the widespread availability of non-invasive computed tomography (CT) and MRI vascular imaging many patients with non-specific neurological symptoms, including dizziness, perhaps even vertigo, end up having CT or MR angiography (MRA), both intracranial and extracranial. Some of these patients have abnormalities in the posterior circulation, but many of these will be asymptomatic and not dangerous. Proximal stenoses such as those at the origin of one vertebral or subclavian artery are potentially symptomatic or dangerous only if the other patients will have normal variants which need to be recognized as such; examples include one large dominant and one small, even vestigial, vertebral artery; one vertebral artery terminating as a posterior inferior cerebellar artery (PICA), not joining the basilar; fenestrations of the basilar; AICA loops in the internal auditory canal adjacent to the vestibulo-cochlear nerve; apparent absence of, or rather failure to image, one PICA or one AICA or one of each. 120,
FIRST ATTACK OF ACUTE SPONTANEOUS VERTIGO
In a patient who suddenly develops, for the first time ever, isolated spontaneous vertigo, nausea, and vomiting the two main diagnoses to consider are vestibular neuritis and cerebellar infarction. Sudden, spontaneous, isolated, unilateral, total, or subtotal loss of peripheral vestibular function is usually ascribed to viral "vestibular neuritis", also called "labyrinthitis", "vestibular neuronitis" and "neuro-labyrinthitis". There evidence for viral infection is slim 6 and some prefer to call it "acute unilateral peripheral vestibulopathy" vertebral artery is vestigial or occluded. Other 17. Corticosteroids given early help recovery of peripheral vestibular function whereas antivirals (i.e. valacyclovir) do not 136.
In patients with combined superior and inferior vestibular neuritis the clinical signs are the same as those that occur after a labyrinthectomy or a vestibular neurectomy. There is a horizontal-torsional spontaneous nystagmus with the slow phases towards the affected ear - that is, quick phases towards the unaffected ear. The nystagmus is always strictly unidirectional - bidirectional gaze-evoked nystagmus excludes the diagnosis. The nystagmus is, to some extent, always suppressed by visual fixation, and for that reason it might be missed on the standard clinical examination. When some means are used to view the eyes in the absence of visual fixation such as ophthalmoscopy with the other eye covered 159 or Frenzel glasses, the nystagmus will be evident in the primary position. The head impulse test (Figure 3) is invariably positive and shows impaired lateral semicircular canal function on the affected side 60.
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Figure 3: The head impulse test. The examiner turns the patient's head as rapidly as possible about 15 degrees to one side and observes the ability of the patient to keep fixating on a distant target. The patient illustrated has a right peripheral vestibular lesion with a severe loss of right lateral semicircular canal function. While the examiner turns the patient's head to toward the normal left side (top row) the patient is able to keep fixating on target. By contrast, when the examiner turns the patient's head to the right the vestibulo-ocular reflex fails and the patient cannot keep fixating on target (E) so that she needs to make a voluntary rapid eye movement-that is, a saccade, back to target (F) after the head impulse has finished; this can be easily observed by the examiner. It is essential that the head is turned as rapidly as possible otherwise smooth pursuit eye movements will compensate for the head turn. |
The patient, although unsteady, can stand without support with the eyes open but rotates toward the side of the lesion when trying to march on the spot with the eyes closed - a positive Fukuda or Unterberger test. There is an ocular tilt reaction, always toward the affected side, but this is rarely obvious clinically: there might be a head tilt toward the affected side and sometimes a vertical diplopia, with the higher image coming from the eye on the side of the affected ear. However, the cardinal sign of the ocular tilt reaction, a conjugate torsional offset of the eyes toward the affected side can only be seen with indirect ophthalmoscopy or with fundus photography. Nevertheless it can be inferred by testing the subjective visual horizontal, an easy test that can be done in any clinical neurophysiology department 62. In some patients the disorder only affects the superior vestibular nerve and spares the inferior division of the vestibular nerve 7 so that the patient with vestibular neuritis is able to develop BPPV presumably as a consequence of otoconia being shed from the utricle into the duct of the posterior semicircular canal 86.
The main differential diagnosis of acute vestibular neuritis is cerebellar infarction and it is possible to tell the difference clinically 4,9,95,98. In the clinical context of a first ever attack of acute spontaneous vertigo, if the head impulse test is positive then the patient has acute vestibular neuritis and if the head impulse test is negative, then the patient does not have acute vestibular neuritis affecting the superior vestibular nerve and might have a cerebellar infarct. With a cerebellar infarct the nystagmus might be bilateral, might be vertical, and will not be well suppressed by visual fixation, that is, it will be obvious even without Frenzel glasses. A patient with a cerebellar infarct usually cannot stand without support even with the eyes open, whereas the patient with acute vestibular neuritis usually can. Acute cerebellar infarcts are obvious on MR but might not be on CT (Figure 4). Some patients with cerebellar infarction will develop potentially lethal, posterior fossa brain oedema requiring emergency neurosurgical decompression 79,90,. Many cases of cerebellar infarction are due to vertebral artery dissection 130 or cardiogenic embolism 63, some paradoxical 69 and these patients might require long-term oral anticoagulation to prevent recurrences 3. Although brainstem infarction, particularly in the AICA territory 140 involving the vestibulo-cochlear nerve and inner ear blood supply 118 and brainstem multiple sclerosis with a plaque involving the vestibulo-cochlear nerve root entry zone 45 might produce an attack with predominantly vertigo and nystagmus there will generally be other, albeit subtle signs to indicate that the process is in the brainstem and not in the labyrinth.
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Figure 4: (a) MRI showing acute infarction in the territory of the medial branch of the left posterior inferior cerebellar artery. The patient presented with acute vertigo and vomiting. On examination the only clinical abnormality was an inability to stand or walk without support. There was no nystagmus and the head impulse test was normal. The MRA was normal. (b) A transoesophageal echocardiogram (showed a small atrial septal defect with spontaneous right to left shunting. |
If the patient has had vestibular neuritis, there is a 1 in 5 chance that he will present later with attacks of typical posterior semicircular canal BPPV or with imbalance due to inadequate vestibular function. If the patient has had a small embolic infarct in the cerebellum, he might not present until he has had another one, this time perhaps not in the cerebellum but elsewhere.
IMBALANCE
Imbalance is not often due to a peripheral vestibular cause. About 20% of patients with imbalance will have chronic vestibular insufficiency due to unilateral or bilateral vestibular loss 127 or due to BPV 94. About 40% will have a single identifiable neurological cause for the imbalance most often: a sensory ataxia due to peripheral neuropathy or myelopathy, an extrapyramidal disorder especially progressive supranuclear palsy (PSP), a cerebellar ataxia either acquired or hereditary, a posterior fossa tumor, normal pressure hydrocephalus or orthostatic tremor. The other 40%, mainly old will have many possible factors such as poor vision, joint replacement, arthritis, maybe presbystasis 10.
Bilateral vestibulopathy. Bilateral vestibular loss causes ataxia and oscillopsia, not vertigo 129 and in the absence of any significant and relevant hearing loss it can cause diagnostic difficulties because an aural cause might not be considered in the differential diagnosis of imbalance. The patient will be able to walk perfectly well heel to toe and the only easily demonstrable abnormality will be an inability to stand, with the eyes closed, but only when trying to do so on a soft, yielding surface such as a mattress or two pillows-a sort of Romberg's test. The head impulse test will be positive to the left, right, up, and down and caloric and rotational tests will show bilaterally absent or severely impaired lateral semicircular canal vestibulo-ocular reflexes. Sometimes patients with severe unilateral loss of vestibular function will present with the same symptoms 149. The most common known cause of bilateral vestibular loss without hearing loss is gentamicin toxicity 61. Systemic gentamicin is not cochleotoxic in human – it does not cause deafness or tinnitus, but as far as the vestibular system is concerned there is no safe dose, and any patient who notices imbalance after a hospital admission has gentamicin vestibulotoxicity until proved otherwise. As the patient might not be aware of having been given gentamicin it might be necessary to requisition the hospital's records. Other causes of isolated bilateral vestibular loss with normal hearing include hereditary vestibulopathy 81 superficial siderosis 87 and meningeal carcinomatosis 124.
Hereditary and episodic cerebellar ataxias
Patients with dominantly inherited spinocerebellar ataxia (SCA) develop, in some combination, progressive limb and gait ataxia, dysarthria and abnormal eye movements. Although horizontal gaze-evoked nystagmus and impaired smooth pursuit can occur in any SCA, in SCA6 there is downbeat nystagmus 50,138,155 or periodic alternating nystagmus 64 but, considering the abnormal smooth pursuit, VOR-suppression is sometimes surprisingly normal 139. Saccades are slow in SCA1 and SCA2 23,25. The vestibular function is bilaterally impaired in SCA1 23,25 and SCA3 52,156 and in typical Friedreich’s ataxia but unlike in SCA, it is accompanied by bilateral deafness 33,44. While the functions of the SCA1, 2 and 3 genes are unknown, it is known that the gene underlying SCA6 codes for the alpha1 sub-unit of a P/Q-type voltage-gated calcium channel, CACNA1A.
Various CACNA1A mutations can also cause an episodic rather than a progressive ataxia - EA2. CACNA1A mutations causing EA2 have been nonsense or splice site or frame-shifts which disrupt the open reading frame, leading to truncated mutant protein products that might be non-functional 80. Several missense mutations that alter single highly conserved amino acid residues can cause EA2 56,137 or severe progressive ataxia 158. The episodes of ataxia lasting hours begin before the age of 20 and are typically triggered by exercise and stress and are relieved by treatment with acetazolamide. Between attacks EA2 patients can have gaze-evoked nystagmus, rebound nystagmus and positional downbeat nystagmus in the head-hanging position that, over time, becomes a spontaneous downbeat nystagmus. Later a mild truncal ataxia develops, along with impaired smooth pursuit and saccadic dysmetria. During attacks, EA2 patients often have some additional spontaneous nystagmus that is not seen during the interictal examination. Some SCA6 patients, like EA2 patients, experience vertigo attacks which also respond to acetazolamide 82.
Patients with EA1 have shorter attacks of ataxia than EA2 patients, have interictal myokymia rather than nystagmus and are usually acetazolamide unresponsive (35, 96). The mutations in EA1 involve a potassium channel gene, KCNA1.
Sporadic and acquired cerebellar ataxia
In some patients late-onset, progressive, sporadic cerebellar ataxias might also have a genetic basis. Some of patients with this type of ataxia also have a progressive bilateral vestibular loss with the characteristic impairment of all smooth compensatory eye movements due to combined loss of vestibulo-ocular reflex and smooth pursuit eye movements 104. These patients might have Multiple System Atrophy (MSA), which can present as a cerebellar ataxia, with or without evidence of autonomic involvement, especially orthostatic hypotension and extrapyramidal features such as bradykinesia and rigidity 152.
The most likely cause of an inexorably progressive, subacute cerebellar ataxia is a paraneoplastic cerebellar degeneration. Some of these patients also have vertigo 88. Anti-neuronal antibodies can sometimes be found 54,132 and when present these can not only help make the diagnosis, they can also narrow the site of the usually occult primary tumor which might be evident on whole body CT or positron emission tomography (PET) scanning 5,12; both these tests can find non-specific lesions or give false-positive results. Creutzfeldt-Jakob disease can present with a similar clinical picture of inexorably progressive subacute cerebellar ataxia 84
Cerebellar ataxia can occur in patients with gluten intolerance (coeliac disease) 1,58. Although doubts have been expressed about the causal relationship 28,153 a gluten-free diet can improve balance. Testing for anti-gliadin antibodies is recommended in patients with imbalance and a positive result is an indication for a small bowel biopsy.
Other rare possible causes of progressive cerebellar ataxia in adults include glutamic acid decarboxylase (anti-GAD) antibodies 70,141 and vitamin E deficiency 71.
In patients with cerebellar ataxia as part of the Wernicke-Korsakoff syndrome there should also be memory and eye movement disorders especially dysarthria and gait ataxia rather than limb ataxia; vestibulo-ocular reflexes can also be abnormal (42). Wernicke-Korsakoff syndrome is due to Vitamin B1 (thiamine) deficiency and is not always due to alcoholism. Acute Wernicke-Korsakoff syndrome is a medical emergency 160.
Extrapyramidal and basal ganglia disorders
Extrapyramidal disorders particularly Progressive Supranuclear Palsy can present with progressive deterioration of gait and balance, axial rigidity and falls 48,112. Later there is dysarthria and bradykinesia and then the characteristic eye movement abnormality: loss of vertical, at first of downward, saccades so that the patient has problems when trying to read or eat 15. Vestibulo-ocular reflex eye movements are unaffected and the patient acquires the characteristic unblinking stare. Later all saccades are lost and swallowing becomes impaired. Life expectancy is less than 5 years. Balance, posture and gait are also involved in typical Parkinson’s disease 110 and in diffuse Lewy body disease 24 with characteristic small rapid steps, difficulty starting, turning and stopping. If the examiner, from behind, quickly pulls the patient back by the shoulders a patient with an extrapyramidal disorder might topple backwards, unless stopped. This is a positive pull test 111. Gait apraxia, lower body Parkinsonism or rather “Primary progressive freezing of gait” refers to elderly patients with profound difficulties in starting and stopping walking and in turning with, at least at first, no motor difficulties moving their legs while supine or with upper limbs or cranial nerves 36. Most develop other extrapyramidal features and are chair-bound within 5 years. Patients with MSA 152 can present with freezing of gait 57 or with dizziness and balance problems 148 due to extrapyramidal or cerebellar dysfunction or orthostatic hypotension.
Balance and gait normally deteriorate with age and deterioration in sensory input, especially vestibular, and the appearance of subcortical white matter changes will only account for about 30% of this deterioration 10.
Sensory ataxia in spinal cord and peripheral nerve diseases
Diseases affecting the dorsal columns of the spinal cord produce proprioceptive impairment in the lower limbs and consequently poor balance on standing and walking – a sensory ataxia. Diseases affecting the dorsal root ganglia, called sensory neuronopathies 92, the dorsal roots themselves or their large myelinated axons in the peripheral nerves can also produce sensory ataxia. In the good old days of syphilis tabes dorsalis was the usual cause. These days vitamin B12 deficiency producing subacute combined degeneration of the spinal cord 66, copper deficiency 91 radiation damage to the spinal cord paraneoplastic sensory neuropathy, Sjogren’s syndrome, coeliac disease, paraproteinemia, chemotherapy especially with platinum compounds and HIV/AIDS all need to be considered in patients with subacute or chronic sensory ataxia. Acute sensory ataxia is common to three eponymous syndromes: Guillain Barre, Miller Fisher and Bickerstaff’s “brainstem encephalitis”. While there are clear clinical differences in these three syndromes, they are all characterised by the presence of serum anti-ganglioside antibodies and all respond to immunotherapy with intravenous gammaglobulin or plasmapheresis.
With sensory ataxias there will be some impairment of distal position and vibration sense. With spinal cord diseases the tendon reflexes in the lower limbs will be brisk and the plantar reflexes extensor, if the pyramidal tracts are also involved. With diseases of the dorsal root ganglia, dorsal roots or peripheral nerves the tendon reflexes will be absent. The traditional Romberg test, standing feet together eyes open and then eyes closed should be positive if the ataxia is to be called sensory. If the patient passes the standard Romberg test, the test can be made more difficult by having the patient stand on a thick foam mat. While this will detect a subtle sensory ataxia it will also detect a vestibular ataxia or rather astancia/astasia and needs further information for correct evaluation.
Nerve conduction studies to look for abnormalities especially of sensory conduction, somatosensory evoked potentials to look especially for abnormalities of spinal cord conduction, cerebrospinal fluid (CSF) examination to look especially for high protein levels, spinal MRI to look for compression or high T2 signal in the dorsal columns and sural nerve biopsy to look for axonal degeneration, demyelination or vasculitis are often needed in addition to blood testing for the diseases mentioned above.
In the elderly, compressive spinal cord and cauda equina problems can present with imbalance and falls and a whole of spine MRI is worth doing in an elderly patient with imbalance and falls for no obvious reason. Nitrous oxide anaesthesia or abuse, usually in the young but sometimes in health professionals, can block vitamin B12 utilization and produce a clinical pattern similar to subacute combined degeneration 74.
Vestibular schwannoma
These days patients with vestibular schwannomas (“acoustic neuromas”) are more likely to have balance problems from the treatment than from the disease. Vestibular schwannomas often grow slowly; the unilateral vestibular loss occurs over years so that patients compensate well and are unlikely to have any symptomatic vestibular ataxia. With MRI scanning of just about everyone with unilateral hearing loss or tinnitus, and those without, small asymptomatic vestibular schwannomas, are, like small pituitary adenomas 27, found incidentally 100. When symptomatic, vestibular schwannomas present with unilateral or asymmetrical bilateral, sensorineural hearing loss or tinnitus 30, or both, to an otologist rather than to a neurologist; however the otologist will not order vestibular function tests, even after MRI shows a vestibular nerve tumor, since the patient has no balance problem 101. If the tumor is then removed, while the patient actually has normal vestibular function, the operation will be like a vestibular nerve section of a normally functioning nerve. There will be an intense post-operative unilateral vestibular deafferentation syndrome with vertigo, vomiting, nystagmus etc and a 25% chance of a mild but permanent ataxia due to chronic vestibular insufficiency 127 needing ongoing vestibular rehabilitation 14,73.
Intracanalicular vestibular schwannomas are best managed with MR monitoring since surgery will inevitably produce total unilateral loss of vestibular and cochlear nerve function. On the other hand letting the tumor grow too far into the cerebello-pontine cistern puts the facial nerve at risk during subsequent surgery 68. Other cerebellopontine angle tumors such as meningiomas and epidermoids cause imbalance only when they large enough to compress the brainstem and cerebellum
Intralabyrinthine vestibular schwannomas are rare but seem to have a propensity to cause vertigo, perhaps through a secondary Meniere-like disorder 113. Hyperventilation-induced nystagmus is a rare but characteristic sign of vestibular schwannoma 106
Cerebellar tumor
Increasing imbalance with headache and positional vertigo is the classic presenting syndrome of cerebellar tumor 67. The positional vertigo is usually persistent rather than paroxysmal 32,55. Patients 4th ventricular tumors such as ependymomas (Figure 5) 102 can have positional vomiting, without any vertigo 31 as well as complex eye movement abnormalities, especially after surgery, including vertical strabismus due to skew deviation rather than a cranial nerve palsy 126.
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Figure 5: MRI from two patients presenting with positional vertigo and progressive ataxia and headache. (a) a 4th ventricular epedymoma and (b) a Chiari malformation. |
In adults, a metastasis is the most common cerebellar tumor and can grow to a considerable size in a cerebellar hemisphere before it causes any problem apart from headache. Acute spontaneous vertigo can occur when there is bleeding into a tumor such as a metastasis or when a cystic tumor such as a hemangioblastoma suddenly enlarges. In such cases everyone gets a nasty surprise once the scan is done. Sometimes it is hard to tell a cerebellar tumor from a cerebellar infarct on CT or MRI; in such cases a PET scan can help. Hydrocephalus, which eventually occurs when cerebellar tumors grow large also, also causes ataxia 135. Recurrent subarachnoid bleeding from cerebellar tumors can produce superficial siderosis with progressive bilateral loss of vestibular and cochlear function 87. Other potential causes of progressive bilateral vestibulo-cochlear loss in cerebellar tumor patients is radionecrosis of the temporal bone 83 and malignant meningitis 72,116,123,146
Chiari malformation
In adults Chiari malformation can cause vestibular and balance problems 133,151 such as cerebellar ataxia, pressure-induced vertigo, positional vertigo, positional nystagmus, often downbeating 13, nystagmus-induced oscillopsia and positional vomiting. Minimal Chiari malformations, like tiny vestibular schwannomas are discovered in patients having MRI for vertigo or non-vestibular symptoms such as headache and it can be hard to decide whether the Chiari in such cases is symptomatic or incidental 2. Herniation through the foramen magnum of the cerebellar tonsils, the human equivalent of the paraflocculus, a part of the vestibulo-cerebellum, appears to be the cause of the balance and vestibular disorders in Chiari malformations. Cerebellar tumors and lumbo-peritoneal CSF shunts can also cause tonsillar herniation and produce a symptomatic acquired Chiari malformation. http://nyneurosurgery.org/chiari_intro.htm
Normal pressure hydrocephalus
Hydrocephalus of any cause can produce imbalance in children and adults. The classical picture of of low or normal pressure hydrocephalus is an elderly person presenting with gait difficulties imbalance, urinary incontinence and failing memory. Imaging shows enlargement of all 4 ventricles with little or no cortical atrophy. CSF pressure is normal although there is increased resistance to CSF inflow with an infusion test 65. CSF diversion with a ventricular shunt can produce a dramatic improvement in balance, memory and continence, although it is hard to predict whether a particular patient will or will not improve 103. The risk of shunting is infection and subdural hemorrhage due to overdraining. If gait and balance improve after 3 days lumbar CSF drainage the patient is more likely to benefit from permanent CSF shunting 135. http://www.neurosurgery.medsch.ucla.edu/Diagnoses/Adult/AdultDis_1.html
Orthostatic tremor
Patients with orthostatic tremor have shaky legs when they stand but not when they walk or sit. Typically the patient can walk around the supermarket normally but cannot stand in the checkout queue. It is a ~16Hz tremor which is present in all the leg muscles when the patient stands but not when contracting the same muscle while sitting. Unlike essential tremor which is an ~ 8Hz tremor affecting the hands and arms and not the legs. Not only can the tremor be recorded with a simple surface EMG (Figure 6) it can also be heard with a stethoscope (sounds like a distant helicopter). Mostly there is no other neurological problem; maybe about 25% also have Parkinsonian features 46. When the tremor becomes disabling treatment with clonazepam, levodopa, etc can be tried, more in hope than expectation. http://orthostatictremor.org/
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Figure 6: Surface EMG of quadriceps during standing in a patient with orthostatic tremor. The typical bursts of activity at 16 Hz are seen. |
SUMMARY
In the patient with repeated attacks of isolated vertigo
(1) Always do a positional test.
(2) Learn to do the particle repositioning manoeuvre.
(3) Always order an audiogram.
(4) Try migraine treatment.
(5) Put vertebrobasilar insufficiency at the bottom of the list.
In the patient having the first ever attack of acute spontaneous
(1) Learn to do the head-impulse test.
(2) Always think of cerebellar infarction.
In the patient who is off-balance
(1) Think of gentamicin vestibulotoxicity.
(2) Think of normal pressure hydrocephalus.
(3) Beware of the posterior fossa tumour or malformation.
(4) Think of orthostatic tremor.
(5) Consider spinal cord or peripheral nerve pathology and do a serum B12.
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