White matter T2 hyperintensity development and clinical deterioration after status epilepticus in a patient with dentatorubral-pallidoluysian atrophy.

Serial T2-weighted magnetic resonance imaging in a 29-year-old woman with juvenile type dentatorubral-pallidoluysian atrophy (DRPLA) demonstrated that a cerebral white matter hyperintensity appeared within 2 months after status epilepticus and persisted for more than 20 months. The patient had rapidly progressive mental regression and became akinetic after status epilepticus. The chronological relationship between the signal changes and the clinical deterioration suggested that the epilepsy, at least in part, contributed to the progression of white matter degeneration, the hallmark of DRPLA.

Proton MR spectroscopy of adult-onset dentatorubral-pallidoluysian atrophy.

PURPOSE: To quantify impairment of the basal ganglia (globus pallidus and thalamus) in adult-onset dentatorubral-pallidoluysian atrophy (DRPLA). METHODS: Five patients with genetically definite adult-onset DRPLA (aged 51 to 65 years, mean 55.6 years) and 5 age- and sex-matched healthy controls underwent conventional magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) of the brain in the voxels predominantly containing the globus pallidus or the thalamus. RESULTS: Conventional MRI studies showed apparently normal intensities in the globus pallidus and thalamus. MRS showed that the choline (Cho)/creatine (Cr) ratio for the patients' globus pallidus, the region preferentially affected in DRPLA, was significantly higher than that in the controls (p<0.05). The N-acetylaspartate (NAA)/Cr ratio for the globus pallidus and the Cho/Cr and NAA/Cr ratios for the thalamus, the region relatively spared in this disease, did not differ significantly between the patients and controls. CONCLUSIONS: MRS may sensitively and specifically detect biochemical alterations in susceptible regions of patients with adult-onset DRPLA.

Expression of the costimulatory molecule BB-1 and its receptors in patients with scleroderma-polymyositis overlap syndrome.

We investigated expression of costimulatory molecules BB-1, B7-1 (CD80), B7-2 (CD86), and their counter-receptors CD28 and CTLA-4 (CD152) in muscle biopsy specimens of patients with scleroderma-polymyositis overlap syndrome (SSc-PM), primary polymyositis (PM), and other related diseases to examine whether the muscle fibers in patients with SSc-PM behave as antigen-presenting cells (APCs). The major histocompatibility (MHC) class II-positive muscle fibers of SSc-PM patients reacted with monoclonal antibodies (mAb) against BB-1 but not against B7-1 or B7-2. The CD4+ T cells expressed the counter-receptors CD28 and CTLA-4, and bound with the BB-1-positive muscle fibers in cell-to-cell contact. Our findings show that muscle fibers in patients with SSc-PM function as "professional" APCs in a way distinct from muscle fibers in patients with primary PM.

Clinical analysis of paraneoplastic encephalitis associated with ovarian teratoma.

BACKGROUND: Recently, paraneoplastic encephalitis associated with ovarian teratoma has been described and related to an autoantibody. METHODS: We describe four patients with ovarian teratoma-associated encephalitis (OTE) and compared their clinical pictures with those of 17 previously reported patients with OTE. RESULTS: Clinically, OTE was characterized by the development of acute prominent psychiatric symptoms (20 of 21 patients), seizures (15 of 21 patients), and central hypoventilation (13 of 21 patients). Our patients had hypersalivation (three patients) and cardiac conduction problems (all patients); hypothermia was present in one patient. The mean time from the onset of OTE to tumor diagnosis was 19.6+/-22.1 weeks. Ventilatory support was required for 54.9+/-25.4 days on average. The white blood cell count in cerebrospinal fluid was 55.1+/-61.2/mm3. Twelve patients showed abnormalities on cranial MRI, involving areas such as the temporal regions (seven patients) or brainstem (four patients). In addition to tumor resection, 17 patients received some type of immunotherapy: 17 patients received corticosteroids, 10 received intravenous immunoglobulins, two received cyclophosphamide, seven received plasma exchange. Eighteen patients with OTE had neurological improvement, including 11 with full recovery. CONCLUSIONS: OTE presents with cardiac conduction problems and hypersalivation in addition to psychiatric symptoms, seizures, and central hypoventilation.

Altered expression of costimulatory molecules in patients with polymyositis.

OBJECTIVE: : The objective of this study was to characterize the involvement of costimulatory molecules in patients with polymyositis (PM). METHODS: : A multiparameter flow cytometry analysis was used to identify peripheral blood mononuclear cell (PBMNC) subsets expressing CD8, CD4, and CD28 in 14 patients with PM, 10 patients with Duchenne muscular dystrophy (DMD), and 10 healthy controls. Patients with PM were divided into the following 2 groups: patients with untreated active PM and patients with posttreated inactive PM. RESULTS: : The percentage of CD8CD28/CD8 T cells and the absolute number of CD8CD28 double-positive T cells was significantly lower in the 9 patients with untreated active PM than in the 5 patients with posttreated inactive PM, the 10 patients with DMD, and the 10 healthy controls. CONCLUSIONS: : Our results show that the CD28 pathway plays a role in PM and that CD8CD28 subsets of PBMNC may represent a useful biomarker of patients with PM.

Calpain-dependent alpha-fodrin cleavage at the sarcolemma in muscle diseases.

To clarify the involvement of calpains in sarcolemmal remodeling, we examined the expression of calpains and their substrate, alpha-fodrin, in various disorders of muscle. Although immunohistological reactions for alpha-fodrin and calpains were weak in normal control muscles, intense immunoreactivity for alpha-fodrin at the sarcolemma and for calpains throughout the cytoplasm were detected in small muscle fibers from patients with inflammatory myositis (IM), rhabdomyolysis (Rhab), and Duchenne muscular dystrophy (DMD). Most of the calpain-alpha-fodrin double-positive muscle fibers in IM and Rhab also expressed the developmental form of myosin heavy chain. The sarcolemma of these small muscle fibers reacted with an antibody that specifically recognizes the 150-kDa fragments of alpha-fodrin (SBDP 150s) cleaved by calpain, but not caspase 3. Western blot analysis confirmed these results. These observations indicate that calpain is activated and reacts with alpha-fodrin as a substrate at the sarcolemma, and plays a key role in modulating sarcolemmal proteins to adapt to the specific conditions in each myopathy.