Bilateral Vestibular Loss

Epidemiology . Bilateral vestibular loss is uncommon. In some patients the cause is known, whereas in other patients the condition seems to be idiopathic, and these patients tend to be older adults.

Pathophysiology . The percentage of patients with ideopathic bilateral vestibular loss varies from 21% to 51%. In the remaining patients the most common cause is ototoxicity, accounting for 17%–66%, with gentamicin being the most common ototoxin. Other causes include bilateral (usually sequential) vestibular neuritis and autoimmune inner ear disease. The underlying pathophysiology is either dysfunction of the peripheral vestibular receptors (as in gentamicin ototoxicity) or dysfunction of the vestibular nerve (as in vestibular neuritis).

Typical presentation . The common complaints are imbalance, disequilibrium, dizziness and oscillopsia (“jumpy vision” or the appearance that the world moves with each step or when riding in a car that goes over a bump). Patients will also be very dependent on their vision for maintaining balance; therefore, falls will often result when trying to walk in the dark, or when closing the eyes in the shower. Depending on the cause, the chronology of symptoms is variable. In idiopathic cases, the development of symptoms may be insidious. In gentamicin ototoxicity, the onset of symptoms usually occurs within several weeks of starting intravenous gentamicin and is unrelated to peak and trough levels. In addition, a mitochondrial genetic mutation on the MT-RNR1 gene confers particular susceptibility to aminoglycoside ototoxicity.

Physical examination . Patients will be obviously unsteady on physical examination. They fail tandem Romberg stance with eyes closed. On dynamic visual acuity testing, they typically lose four or more lines when the head is oscillating in a sinusoidal pattern around the vertical axis compared with when the head is stationary. On fundoscopy, if the head is similarly oscillated, the retinae appear to move (rather than staying entirely steady).

Diagnostic testing . The gold standard test for bilateral vestibular loss is rotary chair testing, which shows the combination of low vestibulo-ocular reflex (VOR) gain and VOR phase lead (more so in the lower frequencies) during sinusoidal harmonic oscillation, and low VOR gain and short vestibular time constants on step velocity testing. Vestibular evoked myogenic potentials are absent. Caloric responses, including ice water calorics, are absent. Video head impulse testing shows low VOR gain bilaterally and overt saccades (if the bilateral loss is recent), or covert saccades (if the bilateral loss is more remote and is now compensated). Computerized dynamic posturography shows a “vestibular” pattern on sensory analysis, as well as an “ankle dominant” pattern (especially in conditions 5 and 6) on strategy analysis. Imaging of the brain and internal auditory canals is usually normal, although when the etiology involves vestibular neuritis, there may be enhancement of the vestibular nerve.

Treatment . Treatment is generally limited to physical therapy for vestibular rehabilitation and strategies for personal safety and fall prevention. These patients can improve but retain significant dependence on vision and proprioception for balance.

Progressive Supranuclear Palsy and Other Atypical Parkinsonisms

Parkinson’s disease and the other parkinsonian disorders often involve disequilibrium at some point in the course of the disease. Idiopathic Parkinson’s disease is by far the most common pathology in this family of diseases but will usually have come to the attention of a neurologist long before referral to a subspecialty clinic of balance disorders. The other diseases in this family include progressive supranuclear palsy (PSP; or the Steele-Richardson-Olszewski syndrome), multiple systems atrophy, corticobasal ganglionic degeneration, and dentatorubropallidoluysian atrophy. Of these, we have selected to focus on PSP because it often presents with disequilibrium early in the course of the disease and may elude diagnosis initially, or be initially misdiagnosed as idiopathic Parkinson’s disease.

Epidemiology . The prevalence of PSP has been estimated variably at 1.39–6.4 per 100,000 and is more common in men. The age of onset is usually 40’s to 60’s.

Pathophysiology . PSP is a tauopathy, and histopathologic studies demonstrate accumulation of abnormal tau protein that is seen as globose neurofibrillary tangles in the prefrontal cortex, globus pallidus, substantia nigra, and subthalamic nucleus.

Typical presentation . By the time the diagnosis is made, symptoms have often been present for several years. Often the initial presentation will be a complaint of unsteadiness or falling, typically backward. Descending stairs sometimes poses a particular challenge. Patients have usually developed some degree of dysphagia by the time the diagnosis is confirmed. Patients with PSP frequently seem to be oblivious to their deficits and consequently exhibit poor judgment regarding their ability to ambulate and to negotiate stairways. As the disease advances, patients become progressively immobilized and are eventually confined to a wheelchair and then to a bed. The mean disease duration from the first onset of symptoms until death is 8.0 ± 4.1 years. Patients usually die within about 5 years of being diagnosed, with death typically resulting from the usual diseases affecting immobilized patients (e.g., aspiration, infections, thromboembolism).

Physical examination . There is usually axial hypertonia manifesting as truncal and neck stiffness (often with tonic hyperextension), although distracting maneuvers (such as having the patient open and close the hands) may be required to elicit this sign. The extremities usually have normal tone initially and lack the resting tremor of Parkinson’s disease, although as the disease advances, symmetrical appendicular hypertonia may develop. Facies eventually become masked; although in contradistinction to Parkinson’s disease, the tone of the periorbital musculature tends to produce the appearance of a “frightened stare.” Oculomotor examination shows obvious slowing down of voluntary vertical saccades, although reflexive vertical saccades may initially be preserved. More subtle findings include convergence insufficiency and square wave jerks. Later in the disease, horizontal saccades are also affected. Cognitive evaluation reveals mild to moderate dementia with apathy and impaired executive function.

Diagnostic testing . Videonystagmography corroborates and quantifies the clinical oculomotor examination. Caloric testing is normal. Rotary chair testing sometimes exhibits “hang-up” of the eyes at the extremes of lateral gaze on optokinetic testing. Sometimes vestibular evoked myogenic potentials are reduced out of proportion to age. MRI sometimes demonstrates midbrain atrophy.

Treatment . Only symptomatic treatment is available. Sometimes a medication for idiopathic Parkinson’s disease (such as levodopa-carbidopa) will bring about a modest, transient response that is never sustained.

Spinocerebellar Ataxias

Epidemiology . The spinocerebellar ataxias (SCAs) are rare and were originally referred to as autosomal dominant ataxias because of their mode of inheritance. They comprise a family of over 20 diseases whose number continues to grow as more forms are recognized. Mutations for most of the SCAs involve trinucleotide repeat expansions, although some are point mutations.

Pathophysiology . Each of the SCAs produces different combinations of pathology in the cerebellum, pons, inferior olives, and spinal cord. The pathology in the cerebellum usually affects Purkinje cells, although SCA3 (Machado-Joseph disease) is an exception in this respect.

Typical presentation . Despite the distinct genetics of each of the SCAs, there is considerable overlap in the clinical presentations. The age of onset is in the 20s’ to 40’s, although SCA6 can present as late as the 60s. Most of the diseases involve gradually progressive ataxia.

Physical examination . Most SCAs exhibit a variety of cerebellar signs, such as dysmetria, dysdiadochokinesia, and dysarthria. Oculomotor signs include saccadic dysmetria (both hypometria and hypermetria), poor smooth pursuit, and spontaneous nystagmus. In some of the SCAs (types 1 and 7), saccades are slow; SCA2 in particular has markedly slow horizontal saccades. The “spinal” component of the “SCAs” often manifests as pyramidal tract signs, such as hyperreflexia and pathological reflexes (Babinski sign, Hoffman sign), although not all of the SCAs exhibit such findings.

Diagnostic testing . The various types of SCAs generally cannot be distinguished on clinical examination alone; genetic testing is available. Occasionally, one finds that a single patient has mutations of two or more SCAs. Imaging often demonstrates progressive cerebellar atrophy. There may also be atrophy of the pons, medulla, and cervical spinal cord.

Treatment . No treatment is available; personal safety and fall prevention are paramount.

Mal de Debarquement

Epidemiology . Mal de debarquement (MDD) is rare, although its incidence is unknown. 95% of patients are middle age females (mean 49.3 years). Migraine is a frequent comorbidity.

Pathophysiology . The pathophysiology is unknown.

Typical presentation . Most cases of MDD seem to be triggered by exposure to motion that is quite prolonged, typically 4 h or more, and consequently the history usually begins after a boat cruise or long train ride. The patient will usually say that the ride was uneventful in that it induced no motion sickness. Immediately after disembarking, the patient has the feeling of “still being on the boat” or train. While many normal people may have this sensation for several hours after such a ride, in patients with MDD the symptoms continue for 6 months to 10 years (mean 3.5 ± 2.5 years). Patients will complain that they always feel as if they are in motion, typically with a rocking or swaying sensation, although a notable exception is that this sensation completely disappears when they ride in a car or other vehicle (including boats). This is an important clue, as virtually no other form of disequilibrium improves when the patient is subjected to additional vestibular stimulation. Occasionally, one sees patients who lack the initial prolonged exposure to motion; however, the history (including improvement with movement and response to benzodiazepines) is otherwise consistent with MDD. Such patients have migraine-associated vertigo as a differential diagnosis.

Physical examination . The physical examination is usually entirely normal.

Diagnostic testing . Diagnostic testing is normal. Occasionally, videonystagmography will show direction-changing positional nystagmus.

Treatment . Because of the rarity of this disease, no systematic studies of its treatment have been conducted. Usually, patients have some response to benzodiazepines, such as clonazepam. A recent study by Dai and colleagues reports that a treatment protocol involving combined simultaneous visual stimuli and motion exposure may bring about “readaptation of the VOR” and thereby diminish the symptoms of MDD, although this finding needs to be replicated.