Dominant spinal muscular atrophy with lower extremity predominance: linkage to 14q32.

OBJECTIVE: Spinal muscular atrophies (SMAs) are hereditary disorders characterized by weakness from degeneration of spinal motor neurons. Although most SMA cases with proximal weakness are recessively inherited, rare families with dominant inheritance have been reported. We aimed to clinically, pathologically, and genetically characterize a large North American family with an autosomal dominant proximal SMA. METHODS: Affected family members underwent clinical and electrophysiologic evaluation. Twenty family members were genotyped on high-density genome-wide SNP arrays and linkage analysis was performed. RESULTS: Ten affected individuals (ages 7-58 years) showed prominent quadriceps atrophy, moderate to severe weakness of quadriceps and hip abductors, and milder degrees of weakness in other leg muscles. Upper extremity strength and sensation was normal. Leg weakness was evident from early childhood and was static or very slowly progressive. Electrophysiology and muscle biopsies were consistent with chronic denervation. SNP-based linkage analysis showed a maximum 2-point lod score of 5.10 (theta = 0.00) at rs17679127 on 14q32. A disease-associated haplotype spanning from 114 cM to the 14q telomere was identified. A single recombination narrowed the minimal genomic interval to Chr14: 100,220,765-106,368,585. No segregating copy number variations were found within the disease interval. CONCLUSIONS: We describe a family with an early onset, autosomal dominant, proximal SMA with a distinctive phenotype: symptoms are limited to the legs and there is notable selectivity for the quadriceps. We demonstrate linkage to a 6.1-Mb interval on 14q32 and propose calling this disorder spinal muscular atrophy-lower extremity, dominant.

Late-onset Tay-Sachs disease: adverse effects of medications and implications for treatment.

The authors conducted a retrospective and brief prospective study of adverse effects of approximately 350 medications in 44 adults with late-onset Tay-Sachs disease (LOTS). Some medications were relatively safe, whereas others, particularly haloperidol, risperidone, and chlorpromazine, were associated with neurologic worsening.

Asymptomatic middle cerebral artery stenosis diagnosed by magnetic resonance angiography.

We reviewed 1440 MRA studies to identify patients with middle cerebral artery stenosis (MCAS). We identified 99 cases, and after reviewing the clinical records, classified 28 as asymptomatic MCAS (AMCAS), a prevalence of 2%. Suspected stroke was the most frequent indication for MRA. Follow-up was available for 21, mean 46.7 months (range 2.4-75.6 months). One stroke occurred in the AMCAS territory (5%), other strokes in five patients (24%). There were five deaths in patients with MCAS; age > 69 (P = 0.045) was the only associated risk factor. This study suggests that patients in whom MRA is performed and shows AMCAS may be at increased risk of strokes in any vascular distribution or of death.

Thrombolytic therapy for acute extra-cranial artery dissection: report of two cases.

Extra-cranial arterial dissection accounts for 10% of strokes in young people. Information on safety of thrombolytic administration in this group is limited. The literature, however, does not favor use of thrombolytics for myocardial ischemia when peripheral arterial dissection coexists. Based on the clinical and radiological features, two patients who presented with acute stroke secondary to arterial dissection were considered for thrombolysis. One of them received intra-venous recombinant tissue plasminogen activator (rtPA), and the other patient received intra-arterial rtPA. There were no post thrombolysis complications. This report supports feasibility of administering thrombolytics in acute ischemic strokes resulting from extra-cranial arterial dissection. Future larger studies are necessary to determine the efficacy, safety and long-term outcome in this patient population.

IgG allotypes and subclasses in Norwegian patients with multiple sclerosis.

Multiple sclerosis (MS) is a multifactorial disease in which genetic and environmental factors apparently have a major influence on the susceptibility and course of the disease. In the present study we have investigated the genetic basis and subclass levels of IgG in MS. Hundred and thirty-six Norwegian patients with MS and 92 controls were genotyped for IgG allotypes of the GM and KM systems. IgG and IgG subclasses were quantified in sera from 115 MS patients and 20 controls. Neither GM nor KM allo-, haplo- or genotypes were significantly correlated with susceptibility, severity or course of the disease. The G1M (3) (3), G2M (23) (23) and G3M (5) (5) allotypes were significantly correlated with high serum levels of IgG3, whereas high IgG2 levels were correlated with G1M (3) (3) and G2M (23) (23) in both patients and controls. Serum levels of IgG subclasses were not significantly correlated with course or severity of the disease. The results indicate no major role for IgG allotypes or IgG subclass levels in the pathogenesis of MS.

Liposuction: procedure for focal volume reduction and body contour remodeling.

Liposuction is the most commonly used procedure for focal reduction of body fat deposits and remodeling the body contour. The procedure consists in aspirating fat from lamellar deposits using a vacuum source connected to a cannula that is passed bluntly through fatty tissue. Adjuncts to the procedure include infiltration of solutions to aid in fat removal or to limit blood loss and the application of ultrasonic energy to lyse fat cells before suction aspiration. Surgical history, theory, procedures, indications, potential complications, and guidelines are discussed herein.

Motor threshold in transcranial magnetic stimulation: a comparison of a neurophysiological method and a visualization of movement method.

Motor threshold is a means of quantifying stimulus in transcranial magnetic stimulation. Two methods are used. One involves neurophysiology techniques and the other is visualization of movement. The aim was to compare the percentage of total machine output (PTMO) necessary to achieve motor threshold using these different methods. Neurophysiological and visualization of movement thresholds were determined in six subjects. In all subjects, the two thresholds were achieved with a < 10% difference in PTMO. Determination of motor threshold with a neurophysiological and a visualization of movement method produced similar results.