Differential subcellular immunolocalization of voltage-gated calcium channel alpha1 subunits in the chinchilla cristae ampullaris.

The immunohistochemical localization of alpha1A, alpha1B, alpha1C, alpha1D and alpha1E voltage-gated calcium channel subunits was investigated in the chinchilla cristae ampullaris and Scarpa's ganglia at the light and electron microscopy level with the use of specific antipeptide antibodies directed against these subunits. The stereocilia membrane of type I and type II hair cells was immunoreactive for alpha1B along its entire length. The basolateral membrane of both types of hair cells was alpha1B, alpha1C and alpha1D immunoreactive.

A novel nonsense mutation in CACNA1A causes episodic ataxia and hemiplegia.

Objective: To identify the disease-causing mutation and to characterize penetrance and phenotypic variability in a large pedigree with episodic ataxia type 2 (EA-2) previously linked to chromosome 19.

Background: Mutations in the CACNA1A gene on chromosome 19 encoding a calcium channel subunit cause EA-2, which is characterized by recurrent attacks of imbalance with interictal eye movement abnormalities.

Methods: The authors used single-strand conformation polymorphism (SSCP) analysis to screen for point mutations, and direct sequencing to identify mutations in CACNA1A.

The dizzy patient.

A patient's history usually contains key information regarding the type of dizziness and the best way to direct diagnostic workup. In dizziness with a vestibular cause (benign positional vertigo, vestibular neuritis, Meniere's disease, migraine, vertebrobasilar insufficiency), patients often describe their world as spinning, whirling, or tilting. Treatment should be directed at the underlying cause whenever possible, and various antivertiginous and antiemetic medications can be used to suppress symptoms.

Internal auditory artery infarction: clinicopathologic correlation.

Objective: To study the pathophysiology of labyrinthine infarction.

Background: The syndrome of sudden onset vertigo or hearing loss is commonly attributed to inner ear vascular disease, yet histologic studies of isolated labyrinthine infarction in humans have been rare and have not included a complete examination of the vertebrobasilar vascular system.

Methods: Temporal bones, brainstem, cerebellum, and the supplying blood vessels were subjected to gross and microscopic postmortem examinations in a 92-year-old woman who had a sudden onset of vertigo and hearing loss in the right ear 7 years before death.

Artemin, a novel member of the GDNF ligand family, supports peripheral and central neurons and signals through the GFRalpha3-RET receptor complex.

The glial cell line-derived neurotrophic factor (GDNF) ligands (GDNF, Neurturin [NTN], and Persephin [PSP]) signal through a multicomponent receptor system composed of a high-affinity binding component (GFRalpha1-GFRalpha4) and a common signaling component (RET). Here, we report the identification of Artemin, a novel member of the GDNF family, and demonstrate that it is the ligand for the former orphan receptor GFRalpha3-RET. Artemin is a survival factor for sensory and sympathetic neurons in culture, and its expression pattern suggests that it also influences these neurons in vivo.

Vertigo.

Vertigo is a subtype of dizziness, which results from an imbalance within the vestibular system. This seminar focuses on three common presentations of vertigo: prolonged spontaneous vertigo, recurrent attacks of vertigo, and positional vertigo. The patient's history is usually the key to differentiation of peripheral and central causes of vertigo.

Oculomotor phenotypes in autosomal dominant ataxias.

Objective: To quantify the oculomotor features of the common spinocerebellar ataxia (SCA) syndromes.

Setting: University ataxia clinic.

Patients: Twenty probands with documented SCA mutations.

Spinocerebellar ataxia type 6 with positional vertigo and acetazolamide responsive episodic ataxia.

The SCA6 mutation, a small expansion of a CAG repeat in a calcium channel gene CACNA1A, was identified in three pedigrees. Point mutations in other parts of the gene CACNA1A were excluded and new clinical features of SCA6 reported--namely, central positional nystagmus and episodic ataxia responsive to acetazolamide. The three allelic disorders, episodic ataxia type 2, familial hemiplegic migraine, and SCA6, have overlapping clinical features.

Familial migraine with vertigo: no mutations found in CACNA1A.

We searched for mutations in the voltage-gated calcium channel gene, CACNA1A, in nine propositi of families with migraine headaches and episodic vertigo inherited in an autosomal dominant pattern. All 47 exons and flanking introns in CACNA1A were subjected to single-strand conformation polymorphism analysis of polymerase chain reaction-amplified genomic DNA. Exons with aberrantly migrating fragments were sequenced using standard techniques.

Motor, cognitive, and behavioral performance following unilateral ventroposterior pallidotomy for Parkinson disease.

Objective: To evaluate the effects of ventroposterior pallidotomy on motor disability and on behavior and cognition in patients with medically intractable idiopathic Parkinson disease.

Design: Detailed motor testing both while receiving and discontinuing levodopa medication, posturography, and neurocognitive and behavioral assessments were performed before and 3 to 6 months after unilateral ventroposterior pallidotomy.

Setting: University-based movement disorder program.

Disequilibrium in older people: a prospective study.

Objective: To identify the clinical and neuroimaging features in older people with disequilibrium of unknown cause.

Background: Many older people show a deterioration of balance without an identifiable cause. Whether the disequilibrium is a normal aging phenomenon, the result of yet unidentified neuropathology, or a combination of the two is unknown.

Expression of neurturin, GDNF, and their receptors in the adult mouse CNS.

Neurturin (NTN) and glial cell line-derived neurotrophic factor (GDNF) are the first two members of the GDNF family (GF) of neurotrophic factors. These two proteins are potent survival factors for several populations of central and peripheral neurons in mature and developing rodents. The receptor for these factors is a multicomponent complex that includes the RET (rearranged during transfection) tyrosine kinase receptor and one of two glycosyl phosphatidylinositol (GPI)-linked ligand-binding components called GDNF family receptor alphas (GFRalpha-1 and GFRalpha-2).

Balance disorders in older persons: quantification with posturography.

We measured sway velocity using static and dynamic posturography in a group of young normal subjects and two groups of subjects older than 75 years; one older group considered their balance normal for their age, and the other reported imbalance. The latter group consisted of patients with documented peripheral and central vestibular disorders and patients with dizziness and imbalance of unknown cause. The velocity of sway was higher in older subjects than in younger subjects and in older subjects who reported imbalance than in age-matched controls.

Differentiating between peripheral and central causes of vertigo.

The history usually provides the key information for distinguishing between peripheral and central causes of vertigo. Probably the only central lesion that could masquerade as a peripheral vestibular lesion is cerebellar infarction because vertigo and severe imbalance may be the only presenting features. MRI is indicated in any patient with acute vertigo and profound imbalance suspected to be the result of cerebellar infarct or hemorrhage.

Dizzy patients: the varieties of vertigo.

Some vertigo results from acute viral labyrinthitis or a cerebrovascular event; many cases are due to loose particulate matter within the semicircular canals. In the vast majority of patients, a careful history and appropriate clinical tests will suffice to identify the cause of the vertigo--and with benign paroxysmal positional vertigo, a simple clinical maneuver can also provide a cure.

Static and dynamic posturography in patients with vestibular and cerebellar lesions.

Objective: To assess the diagnostic usefulness of posturography in 2 well-defined patient groups with impaired balance.

Patients: Ten control subjects, 10 patients with bilateral vestibular loss, and 10 patients with cerebellar atrophy.

Outcome Measures: Amplitude, velocity, and frequency of sway in the anteroposterior and medial-lateral directions on a static platform, on foam, and on a moving platform.

De novo mutation in CACNA1A caused acetazolamide-responsive episodic ataxia.

With the recent report of mutations in the calcium channel gene CACNA1A in two families with episodic ataxia type 2, we investigated a patient with nonfamilial episodic vertigo and ataxia responsive to acetazolamide for similar mutations. Single-strand conformation polymorphism (SSCP) analysis of exon 23 identified an extra band in the patient that was not present in other relatives or in normal controls. Exon 23 of the patient showed a spontaneous C to T substitution at position 4410 resulting in an early stop codon.

Childhood onset of benign positional vertigo.

Benign positional vertigo (BPV) rarely occurs in children, but we identified three members of a family who developed BPV before age 13 years. All three had migraine headaches and two had spontaneous episodes of vertigo. Vasospasm associated with migraine possibly resulted in ischemic damage to the utricular macule, leading to the development of BPV in these patients.

GFRalpha3 is an orphan member of the GDNF/neurturin/persephin receptor family.

GDNF, neurturin, and persephin are transforming growth factor beta-related neurotrophic factors known collectively as the GDNF family (GF). GDNF and neurturin signal through a multicomponent receptor complex containing a signaling component (the Ret receptor tyrosine kinase) and either of two glycosyl-phosphatidylinositol-linked binding components (GDNF family receptor alpha components 1 and 2, GFRalpha1 or GFRalpha2), whereas the receptor for persephin is unknown. Herein we describe a third member of the GF coreceptor family called GFRalpha3 that is encoded by a gene located on human chromosome 5q31.

Dizziness: neurological emergencies.

A patient's medical history provides the key information for deciding on the type of dizziness and its likely cause. First, one must separate vestibular from non-vestibular causes of dizziness to determine the focus of the diagnostic work-up. Of the common causes of vertigo, benign positional vertigo can be reliably diagnosed and cured at the bedside.

A prospective study of posturography in normal older people.

Objective: To follow posturographic measurements over time in a group of normal older subjects to see if sway increases with aging and if sway is greater in those with deteriorating balance and falls.

Subjects: Seventy-two community-dwelling older people (age range 79-91 years), who initially had normal neurological evaluations, were followed with three yearly follow-up examinations.

Measurements: Amplitude and velocity of sway on static and dynamic posturography, Tinetti gait and balance score, reports of falls.

Persephin, a novel neurotrophic factor related to GDNF and neurturin.

A novel neurotrophic factor named Persephin that is approximately 40% identical to glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) has been identified using degenerate PCR. Persephin, like GDNF and NTN, promotes the survival of ventral midbrain dopaminergic neurons in culture and prevents their degeneration after 6-hydroxydopamine treatment in vivo. Persephin also supports the survival of motor neurons in culture and in vivo after sciatic nerve axotomy and, like GDNF, promotes ureteric bud branching.

Deficits of gaze stability in multiple axes following unilateral vestibular lesions.

Abnormalities in the vestibulo-ocular reflex (VOR) after unilateral vestibular injury may cause symptomatic gaze instability. We compared five subjects who had unilateral vestibular lesions with normal control subjects. Gaze stability and VOR gain were measured in three axes using scleral magnetic search coils, in light and darkness, testing different planes of rotation (yaw and pitch), types of stimulus (sinusoids from 0.