Anti-HMGCR myopathy may resemble limb-girdle muscular dystrophy.

Objective: To determine the prevalence and clinical features of anti-HMGCR myopathy among patients with presumed limb-girdle muscular dystrophy (LGMD) in whom genetic testing has failed to elucidate causative mutations. Methods: Patients with presumed LGMD and unrevealing genetic testing were selected based on a few clinico-pathologic features and tested for anti-HMGCR autoantibodies (n = 11). These clinico-pathologic features are peak creatine kinase (CK) greater than 1,000 IU/L and at least 3 of the following features: (1) limb-girdle pattern of weakness, (2) selective involvement of posterior thigh on clinical examination or muscle imaging, (3) dystrophic changes on muscle biopsy, and (4) no family history of muscular dystrophy. Results: Six patients tested positive for anti-HMGCR autoantibodies. In 4, there was a presymptomatic phase, lasting as long as 10 years, characterized by elevated CK levels without weakness. Muscle biopsies revealed variable degrees of a dystrophic pathology without prominent inflammation. In an independent cohort of patients with anti-HMGCR myopathy, 17 of 51 (∼33%) patients were initially presumed to have a form of LGMD based on clinico-pathologic features but were ultimately found to have anti-HMGCR myopathy. Most of these patients responded favorably to immunomodulatory therapies, evidenced by reduction of CK levels and improved strength. Conclusions: Anti-HMGCR myopathy can resemble LGMD. Diagnosis of patients with a LGMD-like presentation of anti-HMGCR myopathy is critical because these patients may respond favorably to immunotherapy, especially those with shorter disease duration.

Abnormal diffusion-weighted magnetic resonance imaging in Creutzfeldt-Jakob disease following corneal transplantations.

BACKGROUND: The value of magnetic resonance imaging of the brain in the diagnosis of iatrogenic cases of Creutzfeldt-Jakob disease has been questioned. OBJECTIVE: To illustrate the value of magnetic resonance imaging of the brain in the diagnosis of iatrogenic Creutzfeldt-Jakob disease. METHODS: Case report. RESULTS: A patient with a history of 3 corneal transplantations exhibited the alien hand sign on initial examination. Diffusion-weighted magnetic resonance imaging of the brain revealed prominent cortical diffusion abnormalities. During the following months, the patient developed rapidly progressive dementia. The diagnosis of Creutzfeldt-Jakob disease was proven by brain biopsy. CONCLUSION: Brain magnetic resonance imaging, particularly diffusion-weighted magnetic resonance imaging, can be very helpful in the diagnosis of Creutzfeldt-Jakob disease, even in suspected iatrogenic cases.

Demyelinating neuropathy in diabetes mellitus.

BACKGROUND: Recent studies have reported that patients with diabetes mellitus (DM) have a predisposition to develop chronic inflammatory demyelinating polyneuropathy (CIDP). OBJECTIVES: To determine whether patients with DM have a polyneuropathy fulfilling electrophysiologic criteria for CIDP, and whether CIDP is more frequent in patients with type 1 than in patients with type 2 DM. METHODS: We prospectively studied the frequency of electrophysiologic changes meeting the criteria for CIDP in patients with DM seen in our electrophysiology laboratory during a 51-month period (period 1). To evaluate the relationship between DM and CIDP, we prospectively determined during a 14-month period (period 2) the frequency of DM in patients seen in our electrophysiology laboratory with other neuromuscular diseases, and the frequency of idiopathic CIDP. RESULTS: During period 1, 120 patients with DM met the electrophysiologic criteria for CIDP (DM-CIDP). The most frequent clinical features of DM-CIDP were those of a predominantly large-fiber sensorimotor neuropathy, with recent motor deterioration and a moderately increased cerebrospinal fluid protein concentration. Twenty-six of the 120 patients were given intravenous immunoglobulin (400 mg/kg per day for 5 days), and 21 patients (80.8%) had significant improvement in the neurologic deficit at the end of 4 weeks of therapy. The DM-CIDP occurred equally in type 1 and type 2 DM. During period 2, 1127 patients were seen. Of these, 189 (16.8%) had DM with various neurologic disorders, including 32 patients (16.9%) with DM-CIDP. Among the remaining 938 patients without DM, 17 (1.8%) had idiopathic CIDP. The odds of occurrence of DM-CIDP was 11 times higher among diabetic than nondiabetic patients (P<.001). CONCLUSIONS: Demyelinating neuropathy meeting the electrophysiologic criteria for CIDP occurred in both types of DM, and its occurrence was significantly higher in diabetic than in nondiabetic patients.

Histopathological changes after microwave coagulation therapy for patients with hepatocellular carcinoma: review of 15 explanted livers.

OBJECTIVES: Microwave coagulation therapy (MCT) is a well established local ablation technique for hepatocellular carcinoma (HCC). However, pathological changes in liver tissue after this therapy have not been well described. We examined the histological changes of HCC after MCT observed in explanted livers in relation to CT findings. METHODS: A total of 15 patients with 18 lesions of HCC underwent MCT and subsequent liver transplantation. Explanted livers were examined macro- and microscopically, and an evaluation of mitochondrial activity of ablated tissue was accomplished by using succinic dehydrogenase (SDH) stain in frozen sections. RESULTS: Of the 18 lesions, 16 were ablated completely and another two had residual tumor. The size of the ablated areas on CT scan corresponded to the macroscopic findings. Histologically the area of ablation was rimmed by a palisading, histiocytic, giant cell, inflammatory reaction associated with fibrotic bands. Coagulative necrosis with faded nuclei and eosinophilic cytoplasm were the predominant findings in the ablated areas. There were also areas in which the tumor cells had cytoplasmic eosinophilia, but nuclei were present and the cells seemed to be viable. On the SDH stain of frozen tissue taken from the edge of the ablated area, SDH activity was negative in both necrotic and nonnecrotic ablated areas. CONCLUSIONS: Most of the treated areas after microwave ablation develop coagulative necrosis accompanied by a foreign body-like inflammatory reaction and fibrosis. Pathologists need to be aware that after this form of therapy, portions of the tumor maintain their native morphological features as if the area is fixed, but their cellular activity is destroyed.