Sensory neuropathy as part of the cerebellar ataxia neuropathy vestibular areflexia syndrome.

OBJECTIVE: The syndrome of cerebellar ataxia with bilateral vestibulopathy was delineated in 2004. Sensory neuropathy was mentioned in 3 of the 4 patients described. We aimed to characterize and estimate the frequency of neuropathy in this condition, and determine its typical MRI features. METHODS: Retrospective review of 18 subjects (including 4 from the original description) who met the criteria for bilateral vestibulopathy with cerebellar ataxia. RESULTS: The reported age at onset range was 39-71 years, and symptom duration was 3-38 years. The syndrome was identified in one sibling pair, suggesting that this may be a late-onset recessive disorder, although the other 16 cases were apparently sporadic. All 18 had sensory neuropathy with absent sensory nerve action potentials, although this was not apparent clinically in 2, and the presence of neuropathy was not a selection criterion. In 5, the loss of pinprick sensation was virtually global, mimicking a neuronopathy. However, findings in the other 11 with clinically manifest neuropathy suggested a length-dependent neuropathy. MRI scans showed cerebellar atrophy in 16, involving anterior and dorsal vermis, and hemispheric crus I, while 2 were normal. The inferior vermis and brainstem were spared. CONCLUSIONS: Sensory neuropathy is an integral component of this syndrome. It may result in severe sensory loss, which contributes significantly to the disability. The MRI changes are nonspecific, but, coupled with loss of sensory nerve action potentials, may aid diagnosis. We propose a new name for the condition: cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS).

Unilateral vestibulotoxicity due to systemic gentamicin therapy.

Systemic gentamicin can cause acute bilateral, simultaneous, symmetrical loss of vestibular function manifested by symptoms and signs of chronic vestibular insufficiency (ataxia and oscillopsia). We report 6 patients presenting with ataxia and oscillopsia, but without a history of vertigo, who had severe unilateral loss of vestibular function on caloric testing. The absence of vertigo in these patients could be explained by two possible mechanisms: either, the unilateral loss of vestibular function was subacute, occurring over several days so that compensation could occur, or bilateral vestibular loss occurred which was then followed by asymmetrical recovery of vestibular function. The second hypothesis is supported by the observation that vestibular hair cells can regenerate after aminoglycoside damage.

Abnormalities of smooth eye and head movement control in Parkinson's disease.

The control of horizontal head and eye movements was examined in 13 nondemented patients with Parkinson's disease (PD) of mild to moderate severity. During pursuit of single-frequency sine waves, smooth component eye velocity was lower in the PD group at frequencies of 1.2 Hz and above; but the differences in overall eye displacement were even greater, indicating an impaired ability to generate catch-up saccades at high frequencies. A corresponding deficit in saccadic performance was observed during a high-frequency saccadic tracking task where predictive saccades of reduced gain and variable timing were generated. During pursuit of pseudo-random target motion with varying degrees of predictability, small differences in smooth component eye velocity were observed, but prediction was otherwise well preserved in the patient group. Vestibulo-ocular reflex (VOR) suppression was also normal during head-free pursuit. No major improvement in smooth pursuit gain could be attributed to drug treatment, based on a comparison of patient results before and after administration of levodopa.

Influence of sensory manipulation on postural control in Parkinson's disease.

Postural control was assessed on a tilting platform system in 20 patients with idiopathic Parkinson's disease and 20 age-matched controls. The amount of information provided by vision and lower limb proprioception was varied during the experiment to investigate the influence of changes in sensory cues on postural control. The patient group with clinical evidence of impaired postural control (Hoehn and Yahr III) had significantly higher sway scores over all sensory conditions than either the Hoehn and Yahr II group or controls. The pattern of sway scores indicated that no obvious deficit in the quality, or processing, of sensory information was responsible for the postural instability observed in this group. The patients in both Hoehn and Yahr groups were also able to respond appropriately to potentially destabilising sensory conflict situations and significantly improved their sway scores when provided with visual feedback of body sway. The results indicate that in Parkinson's disease, the main site of dysfunction in postural control is likely to be at a central motor level.

Coordination of eye and head movements during smooth pursuit in patients with vestibular failure.

During pursuit of smoothly moving targets with combined eye and head movements in normal subjects, accurate gaze control depends on successful interaction of the vestibular and head movement signals with the ocular pursuit mechanisms. To investigate compensation for loss of the vestibulo-ocular reflex during head-free pursuit in labyrinthine-deficient patients, pursuit performance was assessed and compared under head-fixed and head-free conditions in five patients with isolated bilateral loss of vestibular function. Target motion consisted of predictable and unpredictable pseudo-random waveforms containing the sum of three or four sinusoids. Comparison of slow-phase gaze velocity gains under head-free and head-fixed conditions revealed no significant differences during pursuit of any of the three pseudo-random waveforms. The finding of significant compensatory eye movement during active head movements in darkness in labyrinthine-deficient patients, which were comparable in character and gain to the vestibular eye movement elicited in normal subjects, probably explains the similarity of the head-fixed and head-free responses. In two additional patients with cerebellar degeneration and vestibular failure, no compensatory eye movement response was observed, implying that the cerebellum is necessary for the generation of such responses in labyrinthine-deficient patients.

A quantitative study of eye and head movements during smooth pursuit in patients with cerebellar disease.

Eye and head movements were analysed during smooth pursuit in 16 patients with various forms of cerebellar disease. Smooth pursuit gain was reduced across all frequencies and velocities of target motion for the patient group as a whole, during both sinusoidal and pseudo-random target motion. The graded breakdown in the pursuit response, as pseudo-random target motion became less predictable, was of a similar magnitude in patients and controls, implying that the predictive pursuit mechanisms were intact in these patients. During head-free pursuit, when vestibulo-ocular reflex (VOR) suppression was necessary, performance was not significantly different from that observed during head-fixed pursuit in the patient group. This finding is similar to that noted in control subjects, and is consistent with the observation that the VOR gains associated with head movements in darkness were similar in the patient and control groups. The deficits in pursuit and VOR suppression in patients with cerebellar disease therefore represent a decrease in gain in the closed-loop visual feedback pathways with apparent sparing of the predictive pathways.

Cyclosporin A therapy in paraprotein-associated neuropathy.

A case of IgG paraprotein-associated demyelinating neuropathy complicated by respiratory failure, which was unresponsive to standard immunosuppressive drug therapy, is reported. Cyclosporin A therapy resulted in a marked clinical recovery with objective improvement in nerve conduction and vital capacity. The beneficial response suggests that cell-mediated immunity is an important pathogenetic mechanism, and that cyclosporin A may be useful in the treatment of other refractory cases of paraprotein-associated neuropathy.

Visual-vestibular interaction during head-free pursuit of pseudorandom target motion in man.

Recordings of head and eye movement were made during pursuit of mixed-frequency, pseudorandom target motion to study the mechanism of vestibulo-ocular reflex (VOR) suppression during head-free pursuit. When high velocity stimuli were used, slow-phase gaze velocity gains decreased significantly with increases in both absolute target velocity and the velocity ratio between the frequency components. These changes occurred independently of changes in the head displacement gain, which remained relatively constant at the lower frequency and were directly attributable to impaired suppression of the VOR. Similar effects were seen when visual feedback was degraded by tachistoscopic illumination of the target. The results indicate that visual feedback, rather than an efference copy of the head velocity signal, is essential for suppression of slow-phase vestibular eye movement during head-free pursuit. When head-free and head-fixed pursuit were compared, striking similarities were seen for both slow phase gaze velocity gain and phase, indicating that gaze control during smooth pursuit is largely independent of the degree of associated head movement. This suggests that the VOR is not switched off during head-free pursuit. An estimate of the underlying VOR gain was obtained by recording the vestibular response produced by active head movements in darkness. The rather higher estimates of VOR gain obtained using an imaginary earth-fixed target paradigm were found to predict head-free gains more closely than the gains obtained during imaginary pursuit of a moving target, suggesting that such measures may be more representative of the underlying VOR gain.

Vestibulo-ocular reflex suppression during high velocity head-free pursuit in normal subjects.

Recordings of head and smooth pursuit eye movement were made during head-free pursuit of a pseudo-random target motion stimulus. The pseudo-random stimulus was composed of 2 high velocity sinusoids, of frequency 0.4 and 1.3 Hz, with the velocity of the higher frequency being varied as a ratio of the lower frequency velocity between 0 and 2. Slow-phase gaze velocity gain for the lower frequency component decreased significantly with an increase in velocity ratio, and with an increase in target velocity above 60 degrees/s. Gaze velocity gain was frequently less than head displacement gain which remained fairly constant, indicating that the eyes had been driven in the opposite direction to head movement as a result of inability of suppress the vestibulo-ocular reflex. Similar effects were seen when visual feedback was degraded by tachistoscopic illumination of a target composed of 2 low velocity sinusoids (0.11 and 0.13 Hz). These results indicate that visual feedback, rather than head displacement, is essential for suppression of slow-phase vestibular eye movement during head-free pursuit, even at high stimulus velocities.

Small deep cerebral infarcts associated with occlusive internal carotid artery disease. A hemodynamic phenomenon?

Small deep cerebral infarcts, often referred to as lacunes, have been traditionally associated with small-vessel disease affecting the deep penetrating arterial system. We describe 10 cases where these infarcts were associated with severe, ipsilateral internal carotid artery occlusive disease. Seven of these patients also had severe occlusive disease of the contralateral internal carotid artery. The clinical and radiologic features, in combination with studies of cerebral blood flow, were consistent with hemodynamically mediated cerebral ischemia. Occlusive internal carotid artery disease may be more commonly associated with hemodynamic cerebral ischemia than previously believed, and small cerebral infarcts in the deep arterial border zone areas are likely to be an important manifestation of this process.

Idiopathic dystonia and cervical spondylotic myelopathy.

Cervical myelopathy developed in two patients with idiopathic torsion dystonia. There were marked spondylotic changes in both patients, probably attributable to the incessant dystonic movements of the neck. Previous cervical spine surgery may have exacerbated the myelopathy in one of the patients. Cervical myelopathy complicating idiopathic dystonia must be distinguished from other causes of neurological deterioration, since it may be improved by appropriate neurosurgical treatment.

Pyridoxine neuropathy.

A case of sensory neuropathy in a young woman due to long-term ingestion of pyridoxine, with subsequent recovery, is described. Pyridoxine neuropathy may occur after the long-term ingestion of doses as low as 200 mg a day. Because of its widespread use in the community, both the general public and the medical community need to be aware of this recently described complication of megavitamin therapy.

Cryptococcal infections of the central nervous system: a ten year experience.

Twenty cases of cryptococcal CNS infection treated at the Alfred and Fairfield Infectious Diseases Hospitals from 1975 to 1985 were reviewed. A predisposing immunological deficit was present in 40% of the cases and nearly half had evidence of pulmonary involvement. Severe headache was an almost universal presenting feature but fever and meningismus were not. Measurement of CSF cryptococcal antigen and CSF culture were far more reliable diagnostic markers than Indian ink smears. Cerebral CT scanning identified abnormalities in nearly 30% of cases, including 2 with cystic lesions and 2 with mass lesions. Combination therapy with amphotericin B and 5-fluorocytosine was used as first line treatment. Ventricular shunts were required for 2 patients with hydrocephalus, and persistently raised intracranial pressure often required frequent lumbar punctures and corticosteroids for control. Mortality was 30% and correlated with the presence of impaired conscious state, hydrocephalus or other neurological deficit, underlying immunodeficiency and low CSF glucose levels.

Paramedian thalamic and midbrain infarction: the 'mesencephalothalamic syndrome'.

Paramedian infarction in the region of the thalamus and upper midbrain may produce a wide range of neuro-ophthalmological, behavioural and motor abnormalities. The paramedian arteries arise from the first part of the posterior cerebral artery, also known as the basilar communicating artery. The particular arterial topography and its anatomical variation may result in unusual combinations of clinical signs, and infarction may be bilateral in some cases. Diagnosis is often aided by CT scanning and magnetic resonance imaging. Both atherosclerotic occlusion and embolism are thought to be responsible for these particular syndromes. We describe 3 cases that illustrate some of the various clinical features and underlying anatomical vascular arrangements which may be seen in this condition. Thalamic dementia was present in one case with evidence of bilateral thalamic infarction. A complex ophthalmoplegia and hemiparesis were seen in another case, and the third case had a combination of thalamic dementia and ophthalmoplegia.

Paraneoplastic optic neuritis and external ophthalmoplegia.

A 58 year old man developed bilateral optic neuritis and external ophthalmoplegia nine months before presentation with a small cell carcinoma of the lung. There was no evidence of central nervous system metastases and his ocular symptoms responded to corticosteroid therapy.

Wernicke's encephalopathy after prolonged fasting.

Wernicke's encephalopathy has been associated rarely with fasting. We describe a middle-aged patient who presented in a subacute fashion with features of thiamin deficiency after marked weight reduction. Associated features were chest pain, possibly related to cardiac involvement, and a proximal myopathy. The Wernicke-Korsakoff syndrome has been described in the literature for around 100 years. However, the classic triad of ataxia, ophthalmoplegia and impaired conscious state that occurs in a person with chronic alcoholism is by no means its exclusive presentation.