Robert W. Baloh

Benign positional vertigo Clinical and oculographic features in 240 cases

We report the clinical and oculographic features in 240 patients with benign positional vertigo (BPV). In each case, after a rapid position change from the sitting to head-hanging position, a stereotyped torsional paroxysmal positional nystagmus was visually observed and recorded with electronystagmography (ENG). The mean age of onset was 54 years, with a range of 11 to 84 years. In slightly more than one-half of the cases (122/240) a likely diagnosis was determined. The most common identifiable causes were head trauma (17%) and viral neurolabyrinthitis (15%). Females outnumbered males approximately two to one in the idiopathic group. Abnormalities on bithermal caloric testing were found in 47% of patients. Only two patients, both with well-documented neurologic disorders, had central signs on ENG. Our data are consistent with a peripheral, posterior semicircular canal origin of BPV.

Coding and Noncoding Variation of the Human Calcium-Channel β4-Subunit Gene CACNB4 in Patients with Idiopathic Generalized Epilepsy and Episodic Ataxia

Inactivation of the beta4 subunit of the calcium channel in the mouse neurological mutant lethargic results in a complex neurological disorder that includes absence epilepsy and ataxia. To determine the role of the calcium-channel beta4-subunit gene CACNB4 on chromosome 2q22-23 in related human disorders, we screened for mutations in small pedigrees with familial epilepsy and ataxia. The premature-termination mutation R482X was identified in a patient with juvenile myoclonic epilepsy. The R482X protein lacks the 38 C-terminal amino acids containing part of an interaction domain for the alpha1 subunit. The missense mutation C104F was identified both in a German family with generalized epilepsy and praxis-induced seizures and in a French Canadian family with episodic ataxia. These coding mutations were not detected in 255 unaffected control individuals (510 chromosomes), and they may be considered candidate disease mutations. The results of functional tests of the truncated protein R482X in Xenopus laevis oocytes demonstrated a small decrease in the fast time constant for inactivation of the cotransfected alpha1 subunit. Further studies will be required to evaluate the in vivo consequences of these mutations. We also describe eight noncoding single-nucleotide substitutions, two of which are present at polymorphic frequency, and a previously unrecognized first intron of CACNB4 that interrupts exon 1 at codon 21.

Quantitative measurement of saccade amplitude, duration, and velocity

A method for rapid, accurate measurement of saccade amplitude, duration, and velocity (average and maximum) was developed as a functional test of the extraocular motor system. Recordings were made with a direct-current electro-oculographic system, and data analysis was performed on a laboratory digital computer. Saccade amplitude and duration were found to be linearly correlated in 25 normal subjects, with a mean slope of 2.7 msec per degree over a large amplitude range. In the same subjects, saccade amplitude and velocity (maximum or average) had a nonlinear relationship that was best fit by an exponential equation. The two constants of this equation adequately characterized the relationship between saccade amplitude and velocity and permitted rapid statistical comparison between normal and abnormal subjects.

Horizontal semicircular canal variant of benign positional vertigo

We report the clinical features and results of quantitative eye-movement testing in 13 patients with episodic positional vertigo and nonfatiguing direction-changing horizontal positional nystagmus (beating to the right with the head turned to the right and beating to the left with the head turned to the left). The benign history and lack of associated neurologic findings support a peripheral localization of the lesion. This syndrome probably represents a horizontal semicircular canal variant of benign positional vertigo. Free-floating debris in one horizontal canal may explain many of the clinical and oculographic findings.

Migraine‐associated Dizziness

SYNOPSIS

C-terminal truncations in human 3'-5' DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy

Autosomal dominant retinal vasculopathy with cerebral leukodystrophy is a microvascular endotheliopathy with middle-age onset. In nine families, we identified heterozygous C-terminal frameshift mutations in TREX1, which encodes a 3′-5′ exonuclease. These truncated proteins retain exonuclease activity but lose normal perinuclear localization. These data have implications for the maintenance of vascular integrity in the degenerative cerebral microangiopathies leading to stroke and dementias.

Practice parameter: therapies for benign paroxysmal positional vertigo (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.

GLOSSARYAAN = American Academy of Neurology; BPPV = benign paroxysmal positional vertigo; CONSORT = Consolidated Standards of Reporting Trials; CRP = canalith repositioning procedure; NNT = number needed to treat.

Cerebellar infarction presenting isolated vertigo Frequency and vascular topographical patterns

Objective: To determine the frequency of cerebellar infarction mimicking vestibular neuritis (VN), the pattern of clinical presentation, and the territory of the cerebellar infarction when it simulates VN. Methods: We studied 240 consecutive cases of isolated cerebellar infarction in the territories of the cerebellar arteries diagnosed by brain MRI from the acute stroke registry at the Keimyung University Dongsan Medical Center. Results: We identified 25 patients (10.4%) with isolated cerebellar infarction who had clinical features suggesting VN. Two types of cerebellar infarction simulating VN were found: isolated spontaneous prolonged vertigo with imbalance as a sole manifestation of cerebellar infarction (n = 24) and isolated spontaneous prolonged vertigo with imbalance as an initial manifestation of cerebellar infarction (n = 1) followed by delayed neurologic deficits 2 days after the onset. The cerebellar infarction territory most commonly involved was the medial branch of the posterior inferior cerebellar artery territory (24/25: 96%), followed by the anterior inferior cerebellar artery territory (1/25: 4%). None of patients with infarcts in the territory of the superior cerebellar artery or multiple cerebellar arteries showed isolated spontaneous prolonged vertigo. Conclusions: Cerebellar infarction simulating vestibular neuritis is more common than previously thought. Early recognition of the pseudo-vestibular neuritis of vascular cause may allow specific management.

A prospective study of cerebral white matter abnormalities in older people with gait dysfunction

Objectives: The authors previously reported cross-sectional data suggesting a relationship between cerebral white matter hyperintensities (WMH) and gait and balance dysfunction in older people. There have been no longitudinal MRI studies to address this issue. The current study compared progression of WMH in subjects with gait and balance dysfunction with that in healthy subjects. Methods: Two brain MRI were performed on 70 healthy, ambulatory subjects (mean baseline age 79, range 74 to 88) with no identifiable neurologic disease. The mean time between MRI was 4 years. Gait and balance were quantified using the Tinetti Balance and Mobility Scale, and falls were documented each year. On T2-weighted MRI, total hyperintense volume (HV) within three periventricular levels was estimated using the Cavalieri principle, and WMH were graded (0 to 4) using an established semiquantitative scale. Results: Compared with those with normal gait and balance, subjects whose Tinetti scores dropped markedly (>4 points) between first and second MRI showed a significantly greater mean increase in HV during follow-up. The larger group of subjects with an abnormal Tinetti score (<24) at the time of second MRI showed a significantly greater mean increase in HV, compared with those with normal gait and balance at follow-up. Subjects with marked WMH at baseline showed significantly greater increase in HV over time. Subjects with abnormal Tinetti scores had significantly more falls than subjects with normal Tinetti scores. Conclusions: Some older people develop gait and balance dysfunction that is associated with gradual onset of cerebral white matter disease.

Clinical spectrum of episodic ataxia type 2

The authors searched for mutations in CACNA1A in patients with episodic ataxia and describe the clinical spectrum in genetically defined patients. Eighteen families and nine sporadic cases of episodic ataxia were evaluated for mutations in CACNA1A. The families were first genotyped to check for linkage to the chromosome 19p locus of CACNA1A. In families consistent with linkage and in the sporadic cases, the authors screened for polymorphisms in CACNA1A using single-strand conformational polymorphism and denaturing high performance liquid chromatography followed by direct sequencing to identify specific nucleotide changes. Of the 18 families, 11 were linked to 19p and mutations were found in 9. Mutations were detected in four of the nine sporadic cases. Overall, five nonsense mutations, four missense mutations, two deletions, one insertion, and one donor splice mutation were identified. All but two of the 64 genetically defined patients reported episodes of ataxia (two members of one family only had progressive ataxia). All but one had onset before age 20 and all but four had interictal nystagmus. Migraine headaches occurred in more than half, and about two thirds reported a good response to treatment with acetazolamide. Vertigo and weakness accompanied the ataxia in more than half of the genetically defined patients. One family had multiple members with epilepsy. A wide range of mutations in CACNA1A were associated with episodic ataxia. Four of 13 were missense mutations; the remainder predicted truncated proteins. The mutations were scattered throughout the gene, and only 2 of the 13 mutations identified in our laboratory have been reported by other laboratories, so it will not be possible to screen a few “hot spots” in CACNA1A. Overall, the type of mutation, missense versus nonsense, or the location of altered or truncated amino acid residues did not predict the clinical phenotype.