Modification to the approach of the diagnosis of mucous membrane pemphigoid: A case report and literature review

Mucous membrane pemphigoid (MMP) is a subepithelial blistering disease predominantly involving the mucosal surfaces. Distinct subgroups of MMP have recently been identified by using advanced immunopathologic and immunochemical techniques and are described in the literature on the basis of their clinical features and antigenic specificities. Antiepiligrin MMP has been described as an immunochemically distinct entity. Evidence of an existing relationship between malignancy and antiepiligrin MMP has been well documented in the medical literature. This case report illustrates a case of antiepiligrin MMP in a patient with an advanced cancer of the bladder.     

Paraneoplastic chorea associated with CRMP-5 neuronal antibody and lung carcinoma

Paraneoplastic chorea is described in 16 patients: 11 with limited small-cell carcinoma, 2 with lung cancer revealed by imaging, 1 with renal cell carcinoma, and 1 with lymphoma. All had CRMP-5-IgG; 6 also had ANNA-1 (anti-Hu), including 1 without evident cancer. Chorea was the initial and most prominent symptom in 11 patients, asymmetric or unilateral in 5 patients, and part of a multifocal syndrome in 14 patients. Basal ganglia abnormalities were revealed by magnetic resonance imaging and at autopsy (as perivascular inflammation and microglial activation). Four patients improved with chemotherapy, and 2 improved with intravenous methylprednisolone.     

Sympathetic skin response evoked by laser skin stimulation

The objective of this study was to evoke sympathetic skin responses (SSRs) in healthy subjects using laser stimulation and to compare these responses with those induced by conventional electrical stimuli. Twenty healthy subjects were investigated. SSRs were obtained using electrical and laser stimuli delivered to the wrist controlateral to the recording site. The sympathetic sudomotor conduction velocity (SSFCV) was measured in 8 subjects by simultaneously recording the SSR from the hand and the axilla. The latency (L) of the laser-induced SSR (ISSR) was significantly longer than that of the electrically-evoked SSR (eSSR) (mean ISSRL= 1.7 +/- 0.145 ms, mean eSSRL= 1.56 +/- 0.14 ms, p<0.05). The amplitude (A) of the ISSR was lower than the eSSR amplitude (mean ISSRA = 1.31 +/- 0.26 mV, mean eSSRA = 2.59 +/- 0.49 mV, p<0.05). No significant difference between the ISSR and eSSR was observed in either the SSFCV or the variability and reproducibility parameters. Our findings show that SSRs can easily be induced by laser stimuli and that this method shares the technical limitations of conventional eSSRs.     

Shaken infant syndrome: developmental neuropathology, progressive cortical dysplasia, and epilepsy

This study describes the developmental neuropathology of two infants who survived 7 and 9 years, respectively, an episode of violent shaking (shaken infant syndrome) early in their lives. The shaking injuries include cortical and subcortical contusions, hemorrhages, hypoxic/ischemic and axonal damage, and severe edema. The types, distribution, and resolution of these shaking injuries are detailed by sequential radiographic studies and by pathologic examination at postmortem. Despite their severity and extent, these injuries resolved in a relatively short period of time. By 6 months, the original injuries are repaired and the resultant encephaloclastic encephalopathies (e.g., multicystic encephalomalacia, porencephaly, generalized white matter attenuation, diffuse cortical atrophy, microgyria, ulegyria, and hydrocephalus ex vacuo) are well established. No appreciable pathologic differences are detected when radiographic findings at 6 months of age are compared to postmortem observations. On the other hand, undamaged and/or partially damaged cortical regions survive the original insult and undergo post-injury reorganization that transforms the residual cortex structural and presumably functional organization. Prominent features of this post-injury reorganization include progressive cortical dysplasia with cytoarchitectural disorganization, laminar obliteration, morphologic and functional (synaptic reorganization) transformation of some neurons, preservation of layer 1 intrinsic fibers and Cajal-Retzius cells, and the presence of large (hypertrophic) intrinsic neurons with intense neurofilament immunoreactivity. We propose that this progressive dysplastic process modifies the residual cortex structural and functional organization, influences the child's neurological and psychological maturation, and may play a significant role in the pathogenesis of ensuing neurological and/or psychological sequelae.     

Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination

Multiple sclerosis (MS) is a disease with profound heterogeneity in clinical course, neuroradiological appearance of the lesions, involvement of susceptibility gene loci, and response to therapy. These features are supported by experimental evidence, which demonstrates that fundamentally different processes, such as autoimmunity or virus infection, may induce MS-like inflammatory demyelinating plaques and suggest that MS may be a disease with heterogeneous pathogenetic mechanisms. From a large pathology sample of MS, collected in three international centers, we selected 51 biopsies and 32 autopsies that contained actively demyelinating lesions defined by stringent criteria. The pathology of the lesions was analyzed using a broad spectrum of immunological and neurobiological markers. Four fundamentally different patterns of demyelination were found, defined on the basis of myelin protein loss, the geography and extension of plaques, the patterns of oligodendrocyte destruction, and the immunopathological evidence of complement activation. Two patterns (I and II) showed close similarities to T-cell-mediated or T-cell plus antibody-mediated autoimmune encephalomyelitis, respectively. The other patterns (III and IV) were highly suggestive of a primary oligodendrocyte dystrophy, reminiscent of virus- or toxin-induced demyelination rather than autoimmunity. At a given time point of the disease--as reflected in autopsy cases--the patterns of demyelination were heterogeneous between patients, but were homogenous within multiple active lesions from the same patient. This pathogenetic heterogeneity of plaques from different MS patients may have fundamental implications for the diagnosis and therapy of this disease.     

De novo mutation in the Notch3 gene causing CADASIL

CADASIL, an autosomal dominant arteriopathy responsible for stroke and dementia, is caused by strongly stereotyped mutations in the Notch3 gene. We report a patient with a condition strongly suggestive of CADASIL (migraine, stroke, and white matter abnormalities), except that this patient did not have any first-degree relatives with similar symptoms. This patient carried a heterozygous Arg182Cys mutation in the Notch3 gene; this mutation was absent in his two biological parents. These data demonstrate the occurrence of a de novo noninherited mutation in the Notch3 gene, which indicates that CADASIL should not be rejected in the absence of a family history. Therefore, our finding suggests that CADASIL may be more frequent than anticipated.