Search PubMed⌕ Search

Biomedical subjects

R W Baloh

Publications and source records attributed to R W Baloh.

At least 37 records · Page 2Linked to original sources
PubMed2003

Sudden bilateral simultaneous deafness with vertigo as a sole manifestation of vertebrobasilar insufficiency.

A 68 year old woman presented with bilateral sudden simultaneous hearing loss and transient spontaneous vertigo as a sole manifestation of vertebrobasilar insufficiency. Extensive investigation to exclude other causes was unremarkable. Magnetic resonance imaging of the brain, including diffusion images, showed no abnormalities. A magnetic resonance angiogram showed severe stenosis of the middle third of the basilar artery. A pure tone audiogram showed moderate sensorineural-type hearing loss bilaterally. The localisation and mechanism of an isolated cochleovestibular dysfunction are discussed.

Aged↗
PubMed2002

Familial horizontal gaze palsy with progressive scoliosis maps to chromosome 11q23-25.

Horizontal gaze palsy with progressive scoliosis (HGPS) is a rare, autosomal recessive disorder characterized by a congenital absence of conjugate horizontal eye movement, with progressive scoliosis developing in childhood or adolescence. The authors identified two unrelated consanguineous families with HGPS. Genomewide homozygosity mapping and linkage analysis mapped the disease locus to a 30-cM interval on chromosome 11q23-25 (combined maximum multipoint lod score Z = 5.46).

Adolescent↗
PubMed2001

Loss-of-function EA2 mutations are associated with impaired neuromuscular transmission.

OBJECTIVE: To examine the functional consequences of episodic ataxia type 2 (EA2)-causing nonsense and missense mutations in vitro and to characterize the basis of fluctuating weakness in patients with E2A. BACKGROUND: Mutations in CACNA1A encoding the Ca(v)2.1 calcium channel subunit cause EA2 through incompletely understood mechanisms. Although the Ca(v)2.1 subunit is important for neurotransmission at the neuromuscular junction, weakness has not been considered a feature of EA2. METHODS: The disease-causing mutations in three unrelated patients with EA2 and fluctuating weakness were identified by mutation screening and sequencing. Mutant constructs harboring mutations R1281X, F1406C, R1549X were transfected into COS7 cells and expressed for patch clamp studies. Single-fiber electromyography (SFEMG) was performed in patients to examine synaptic transmission at the neuromuscular junction. RESULTS: Functional studies in COS7 cells of nonsense and missense EA2 mutants demonstrated markedly decreased current densities compared with wild type. SFEMG demonstrated jitter and blocking in these patients with EA2, compared with normal subjects and three patients with SCA-6. CONCLUSION: EA2-causing missense and nonsense mutations in CACNA1A produced mutant channels with diminished whole cell calcium channel activity in vitro due to loss of function. Altered biophysical properties or reduced efficiency of plasma membrane targeting of mutant channels may contribute to abnormal neuromuscular transmission, manifesting as myasthenic syndrome.

Calcium Channels↗
PubMed2001

Drop attacks in older patients secondary to an otologic cause.

The clinical features and treatment of seven patients with drop attacks attributable to inner ear disease presenting after age 65 are described. A neurologic or cardiovascular cause of drop attacks was initially suspected. Audiovestibular testing documented a unilateral inner ear disorder. The salient clinical features of these cases are discussed. The patients underwent ablative vestibular surgery, and all compensated well and were free of vertigo and falls up to 10 years postoperatively.

Aged↗
PubMed2001

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.

Accidental Falls↗
PubMed2001

Hereditary vascular retinopathy, cerebroretinal vasculopathy, and hereditary endotheliopathy with retinopathy, nephropathy, and stroke map to a single locus on chromosome 3p21.1-p21.3.

We performed a genomewide search for linkage in an extended Dutch family with hereditary vascular retinopathy associated with migraine and Raynaud phenomenon. Patients with vascular retinopathy are characterized by microangiopathy of the retina, accompanied by microaneurysms and telangiectatic capillaries. The genome search, using a high throughput capillary sequencer, revealed significant evidence of linkage to chromosome 3p21.1-p21.3 (maximum pairwise LOD score 5.25, with D3S1578). Testing of two additional families that had a similar phenotype, cerebroretinal vasculopathy, and hereditary endotheliopathy with retinopathy, nephropathy, and stroke, revealed linkage to the same chromosomal region (combined maximum LOD score 6.30, with D3S1588). Haplotype analysis of all three families defined a 3-cM candidate region between D3S1578 and D3S3564. Our study shows that three autosomal dominant vasculopathy syndromes with prominent cerebroretinal manifestations map to the same 3-cM interval on 3p21, suggesting a common locus.

Chromosome Mapping↗
PubMed2001

Familial benign recurrent vertigo.

Benign recurrent vertigo (BRV) has been previously linked to migraine but there have been no prior studies of families with BRV. We studied the families of 24 patients who presented to our clinic with BRV and who reported a family history of similar attacks of vertigo. All probands underwent diagnostic evaluation to exclude identifiable causes of recurrent vertigo and they completed a standardized medical questionnaire pertaining to episodic vertigo and the features of migraine. This questionnaire was also sent to all relatives of the probands who agreed to participate. Of 220 relatives who returned questionnaires, 37% reported BRV and 50% met the diagnostic criteria for migraine. By contrast, only one of 43 (2%) unrelated spouses reported BRV and 10 of 43 (23%) met the diagnostic criteria for migraine. More than two-thirds of relatives with BRV met the diagnostic criteria for migraine and the majority reported that they had a typical migraine headache with at least some of their episodes of vertigo. Both BRV and migraine showed a female preponderance (more than 2 to 1). Familial BRV seems to be a migraine syndrome, probably inherited in an autosomal dominant fashion with decreased penetrance in men. In the search for the causative gene, vertigo may be a more useful marker than migraine because recurrent vertigo is relatively rare in the general population whereas migraine is very common.

Adult↗
PubMed2001

Prosper Ménière and his disease.

In 1861, Prosper Ménière presented a paper before the French Academy of Medicine in which he described a series of patients with episodic vertigo and hearing loss. He also mentioned the postmortem examination of a young girl who experienced vertigo after a hemorrhage into the inner ear. Prior to that time, vertigo was thought to be a cerebral symptom similar to epileptic seizures. Ménière pointed out that vertigo frequently had a benign course and that common treatments, such as bleeding, often did more harm than good. He was not attempting to define a disease or syndrome but rather to emphasize that vertigo could originate from damage to the inner ear. Confusion regarding the clinical and pathologic features of Ménière disease persisted well into the 20th century.

Academies and Institutes↗
PubMed2001

Slowing of voluntary and involuntary saccades: an early sign in spinocerebellar ataxia type 7.

We describe quantitative oculomotor findings in a patient with subclinical spinocerebellar ataxia type 7 (SCA7) and a borderline mutation of 38 CAG repeats and her daughter with SCA7 and 46 repeats. Both subjects demonstrated significant slowing of voluntary and involuntary saccades, but retinal examination was normal. Smooth pursuit and fixation suppression of VOR were mildly impaired. Slow saccades may be the earliest neurologic finding even in asymptomatic SCA7 patients with normal ocular fundi. The SCA7 mutation probably has an early impact on brainstem fast eye movement centers.

Adult↗
PubMed2001

Impairments in the initial horizontal vestibulo-ocular reflex of older humans.

To determine age-related changes, the initial horizontal vestibulo-ocular reflex (VOR) of 11 younger normal subjects (aged 20-32 years) was compared with that of 12 older subjects (aged 58-69 years) in response to random transients of whole-body acceleration of 1,000 and 2,800 degrees/s2 delivered around eccentric vertical axes ranging from 10 cm anterior to 20 cm posterior to the eyes. Eye and head positions were sampled at 1,200 Hz using magnetic search coils. Subjects fixed targets 500 cm or 15 cm distant immediately before the unpredictable onset of rotation in darkness. For all testing conditions, younger subjects exhibited compensatory VOR slow phases with early gain (eye velocity/head velocity, interval 35-45 ms from onset of rotation) of 0.90 +/- 0.02 (mean +/- SEM) for the higher head acceleration, and 0.79 +/- 0.02 for the lower acceleration. Older subjects had significantly (P < 0.0001) lower early gain of 0.77 +/- 0.04 for the higher head acceleration and 0.70 +/- 0.02 for the lower acceleration. Late gain (125-135 ms from onset of rotation) was similar for the higher and lower head accelerations in younger subjects. Older subjects had significantly lower late gain at the higher head acceleration, but gain similar to the younger subjects at the lower acceleration. All younger subjects maintained slow-phase VOR eye velocity to values > or = 200 degrees/s throughout the 250-ms rotation, but, after an average of 120 ms rotation (mean eccentricity 13 degrees), 8 older subjects consistently had abrupt declines (ADs) in slow-phase VOR velocity to 0 degree/s or even the anticompensatory direction. These ADs were failures of the VOR slow phase rather than saccades and were more frequent with the near target at the higher acceleration. Slow-phase latencies were 14.4 +/- 0.4 ms and 16.8 +/- 0.4 ms for older subjects at the higher and lower accelerations, significantly longer than comparable latencies of 10.0 +/- 0.5 ms and 12.0 +/- 0.6 ms for younger subjects. Late VOR gain modulation with target distance was significantly attenuated in older subjects only for the higher head acceleration.

Acceleration↗
PubMed2001

Vertigo and the enlarged vestibular aqueduct syndrome.

An enlarged vestibular aqueduct (EVA) is one of the most commonly identified inner ear bony malformations in children with sensorineural hearing loss of unknown cause. Most previous reports have focused on hearing loss, but individuals with EVA may also experience paroxysmal vertigo lasting minutes to hours. We report the clinical vestibular features and vestibular function testing of two children and one adult with EVA who had a history of sensorineural hearing loss and presented to our Neurotology Clinic for the evaluation of episodic vertigo. All the patients had an antecedent history of profound bilateral sensorineural hearing loss that had been present since early childhood. The onset of vertigo was delayed into adulthood in one patient. Episodes of vertigo could be triggered by minor head trauma or vigorous physical activity. Despite recurrent episodes of vertigo, vestibular function was normal or moderately impaired compared with the severe auditory deficit. Careful analysis of temporal bone CT demonstrated EVA. Associated enlargement of the membranous endolymphatic sac was evident on brain MRI. While hearing loss is a prominent symptom in patients with EVA, vestibular symptoms may cause referral to a neurologist. Although hearing loss occurs early in childhood, vestibular symptoms can be delayed into adulthood, a finding not previously reported.

Age of Onset↗
PubMed2001

Otolith function in cerebellar ataxia due to mutations in the calcium channel gene CACNA1A.

The vestibulo-ocular reflexes stabilize retinal images during head movements. While there is a wealth of information about the interaction between the cerebellum and vestibulo-ocular reflexes mediated by the semicircular canals, little is known about the role of the cerebellum in the generation of the otolith-mediated linear vestibulo-ocular reflex (LVOR). By means of transient linear acceleration of the whole body along the interaural axis, we examined the LVOR in six patients with hereditary cerebellar ataxia due to mutations of the calcium channel gene CACNA1A, five with spinocerebellar ataxia type 6 (SCA6) and one with episodic ataxia type 2 (EA-2). Six age-matched normal subjects served as controls. Using a peak acceleration of 0.5 g in combination with recording by the binocular scleral magnetic search coil method, it was possible to study the latency and sensitivity of the LVOR in the first 150 ms after motion onset. The normal LVOR showed a significant dependence on viewing distance and covaried with vergence angle, and could be enhanced by the presence of a visible target. In contrast, the LVOR of ataxic patients had normal latency but significantly decreased sensitivity that was not enhanced with visible or nearer targets despite normal vergence. Substituting for the normal smooth LVOR slow phase, ataxic patients employed catch-up saccades 150-250 ms after motion onset. These findings suggest a critical role of the cerebellum in the modulation of otolith-ocular signals that is independent of motor vergence.

Adult↗
PubMed2001

Harold Schuknecht and pathology of the ear.

BACKGROUND: Like Joseph Toynbee and Karl Wittmaack before him, Harold Schuknecht understood that studying pathology was the key to advancing the scientific basis of neurotology. His work elucidated the pathophysiology of the most common neurotologic disorders, including benign paroxysmal positional vertigo, Meniere's disease, and viral neurolabyrinthitis. Schuknecht was a tireless crusader against medical and surgical treatments that he considered to have little scientific foundation. His textbook Pathology of the Ear remains the definitive work in the field.

Ear↗
PubMed2001

Brain volume changes on longitudinal magnetic resonance imaging in normal older people.

BACKGROUND AND PURPOSE: The purpose of this study is to investigate the longitudinal age-related changes in human brain volume using stereological methods. METHODS: Sixty-six older participants (34 men, 32 women, age [mean +/- SD] 78.9 +/- 3.3 years, range 74-87 years) with normal baseline and follow-up examinations underwent 2 MRIs (magnetic resonance imaging) of the brain on average 4.4 years apart. The volumes of the cerebrum (defined as cortex, basal ganglia, thalamus, and white matter), lateral ventricles, and cerebellum were estimated on the 2 MRIs using an unbiased stereological method (Cavalieri principle). RESULTS: The annual decrease (mean +/- SD) of the cerebral volume was 2.1% +/- 1.6% (P < .001). The average volume of the lateral ventricles on the second MRI was increased by 5.6% +/- 3.6% per year (P < .001). The average volume of the cerebellum on the second MRI was decreased by 1.2% +/- 2.2% per year (P < .001). Even though the average cerebral volume was significantly different between men and women on initial MRI and second MRI, the percentage change of the age-related cerebral volume decrease in male and female brains between initial MRI and second MRI were identical. CONCLUSIONS: The findings showed that there was age-related atrophy of cerebrum and cerebellum and age-related disproportional enlargement of lateral ventricles in normal older men and women.

Aged↗
PubMed2001

Age-related changes in vestibular function: a longitudinal study.

The objective of this study was to identify age-related changes in the vestibulo-ocular reflex (VOR) in normal older subjects and patients complaining of disequilibrium followed serially over time. Cross-sectional studies have found decreases in vestibular function in older subjects compared to younger subjects, but no prior longitudinal studies have been made following the same older subjects over time. We measured VOR responses using step and sinusoidal stimuli in 110 normal subjects and 51 patients with disequilibrium of unknown cause. This report focuses on 57 normal subjects who were able to return for five yearly examinations and 7 patients who were found to have severe bilateral vestibulopathy on the initial examination. In the normal subjects, there was a significant shortening of the VOR time constant to step changes in angular velocity and an amplitude-dependent decrease in gain and increase in phase lead of low-frequency sinusoidal responses over the five examinations. There was also a decrease in the gain of visual-vestibular responses at low frequencies of sinusoidal stimulation over the five examinations. The patients with bilateral vestibulopathy showed relatively little change in vestibular function over the five years of follow-up. This is the first longitudinal study to show age-related decreases in vestibular responses in normal older subjects. The VOR changes identified were not associated with symptoms or signs of disequilibrium. A small subgroup of patients with disequilibrium of unknown cause had profound bilateral vestibulopathy that remained stable during follow-up. These patients likely had an underlying disease even though in most cases the disease process could not be identified.

Aged↗