Adult onset distal and proximal myopathy with complete ophthalmoplegia associated with a novel de novo p.(Leu1877Pro) mutation in MYH2.

An MYH2 mutation p.(Glu706Lys) was originally described in a family with autosomal dominant inheritance, where the affected family members presented with multiple congenital contractures and ophthalmoplegia, progressing to a proximal myopathy in adulthood. Another patient with a dominant mutation p.(Leu1870Pro) was described, presenting as a congenital myopathy with ophthalmoplegia. Here, we present a patient with symptoms beginning at age 16 years, of prominent distal but also proximal weakness, bulbar involvement and ophthalmoplegia. Initially, clinically classified as oculopharyngodistal myopathy, the patient was found to carry a novel, de novo MYH2 mutation c.5630T>C p.(Leu1877Pro). This expands the phenotype of dominant MYH2 myopathies with the clinical phenotype overlapping the oculopharyngodistal myopathy spectrum.

Intraneural perineurioma.

Intraneural perineurioma is a rare tumour that affects peripheral nerves and, based on its histological features, may be confused with hereditary motor and sensory neuropathies. Detailed neuropathology, including immunoperoxidase stains and electron microscopy, is vital to distinguish these conditions. We report two patients with intraneural perineurioma that demonstrate salient features of this tumour. The first patient is the longest reported follow-up of an intraneural perineurioma; extension of the lesion was observed over 14years. The second patient is an 11-year-old female whose treatment highlights some of the controversy surrounding the management of these lesions, and the importance of thorough macroscopic and microscopic assessment by pathologists, including the status of surgical resection margins.

Lethal X-linked microcephaly with dysmorphic features, bilateral optic pathway aplasia and normal eyes.

We describe a family, consisting of two brothers and a maternal uncle who died of an apparently identical condition, within a few days of birth, suggestive of an X-linked mode of inheritance. The propositus (the older sibling) was investigated in detail and showed the following clinical features: microcephaly, facial dysmorphism, malformations of hands and feet, and cryptorchidism. Examination of the brain revealed arhinencephaly, a primitive gyral pattern, arrested cortical maturation, absence of corticofugal tracts and corpus callosum, agenesis of the optic pathway with preserved eyes and oculomotor system, absent auditory pathway, agenesis of the pars compacta of the substantia nigra and severe hypoplasia of the cerebellum and its connections. This family belongs to the group of X-linked microcephalies and has some features in common with the Juberg-Marsidi syndrome. The fact that the CNS abnormalities were incompatible with life and the facial dysmorphic features were quite different makes it unlikely that the affected individuals in this family had Juberg-Marsidi syndrome. However, this does not exclude the possibility that more restricted anterior induction defects may occur in some X-linked microcephalies such as Juberg-Marsidi syndrome resulting in prolonged survival.

Ganglioglioma of the optic chiasm: case report and review of the literature.

We report a case of a hypothalamic chiasmatic ganglioglioma in a 21-year-old woman who presented with hyperprolactinemia and developed visual field defects. This circumscribed cystic lesion with an enhancing mural nodule was radiologically indistinguishable from a pilocytic astrocytoma. Although rare, gangliogliomas should be included in the differential diagnosis of lesions occurring in this area of the brain.

Herpes zoster brachial plexus neuritis.

This is the first report of brachial plexus inflammation associated with clinical herpes zoster paresis. A 78-year-old female with a 3-week history of herpes zoster of the C4, C5, and C6 dermatomes developed left upper arm monoplegia. She died from an acute myocardial infarction. Post-mortem provided a rare opportunity to study the neuropathology of herpes zoster motor involvement. Histology of the brachial plexus showed extensive lymphocytic infiltration, myelin breakdown, and preservation of axons without vasculitis. The cervical spinal cord showed perivascular lymphocytic cuffing and no anterior horn necrosis. We suggest, the brachial plexus inflammation was a distal extension of a dorsal ganglionitis. Brachial plexus neuritis may be a direct cause of reversible upper limb paresis in herpes zoster. We demonstrate the motor neuropathy is an inflammatory demyelinative process consistent with the recovery observed in a number of patients. We postulate post-herpetic neuralgia may be related to an ongoing inflammatory process.

Collecting duct carcinoma of the kidney: a report of three cases and review of the literature.

Collecting duct carcinoma (CDC) of the kidney is a rare neoplasm arising from the medullary collecting ducts. The clinicopathological features of three cases are here presented to add to the 42 cases reported so far in the English language literature. Hematuria is the most common presenting symptom, although 10% of patients present with metastatic disease, often in neck lymph nodes. The tumor mass is typically centred on the medulla of the kidney and extends into the cortex. Radiological diagnosis may be difficult because the radiological features of CDC are poorly described. The histological appearances have been described as tubulo-papillary, tubular, solid and sarcomatoid. Intracytoplasmic mucin may be present. The typical immunohistochemical profile is positive staining with antibodies for low and high molecular weight keratin and epithelial membrane antigen (EMA) and positive staining with the lectin Ulex europaeus agglutinin. Literature reports of cytogenetic characterisation show loss of chromosomes resulting in monosomies. Prognosis is poor as more than half of the reported cases have developed metastases or died within two years of presentation.

Alzheimer's disease and apolipoprotein E genotype in Western Australia: an autopsy-verified series.

OBJECTIVE: To determine the relationship between the apolipoprotein E epsilon 4 allele and autopsy-verified Alzheimer's disease (AD) in an Australian population. DESIGN: Retrospective case-control study. SETTING: Royal Perth Hospital, Perth, Western Australia (a tertiary referral hospital). SUBJECTS: 50 subjects with "definite" AD (according to the histological and clinical criteria of the Consortium to Establish a Registry for Alzheimer's Disease [CERAD]) and 30 control subjects who had died from a non-neurological disease were randomly selected from the hospital's neuropathology register. OUTCOME MEASURES: Histological grading of brain sections stained with the modified Bielschowsky stain according to the criteria of CERAD; number (burden) of neuritic plaques; apolipoprotein E genotype (APOE). RESULTS: Frequency of the epsilon 4 allele was significantly higher in the AD group (37%) than in the control group (2%) (chi 2 = 25.8; P < 0.00001). In the AD group, 50% of subjects were heterozygous for the epsilon 4 allele and 12% were homozygous, while in the control group one subject was heterozygous for the allele and none were homozygous. No association was seen between the epsilon 4 allele and neuritic plaque burden in the hippocampus, entorhinal cortex, middle frontal gyrus or inferior parietal lobule in subjects with AD. CONCLUSIONS: Our findings confirm an association between the epsilon 4 allele and autopsy-verified AD. The epsilon 4 allele may be an important risk factor for susceptibility to AD in the general Australian population.

Skeletal manifestations of primary oxalosis.

We describe the clinical, radiographic and histological features of skeletal involvement in four patients with end-stage renal failure due to primary oxalosis. The clinical features were unrelenting bone pain, and in two patients multiple fractures. Radiographic features were, in chronological order: (1) radiodense metaphyses and other red marrow bone; (2) cortical defects in metaphyses; (3) spontaneous fracture-separations of epiphyses of long limb bones which healed poorly. The fractures occurred through crystal deposits, and fracture displacement was associated with extrusion of crystalline material from bone. On histological examination crystals were found to replace metaphyseal bone. Pericrystalline giant cell granulomata replaced bone marrow. Erosion surfaces near granulomas were increased. Subperiosteal and intra-osseous tophi of calcium oxalate were seen. Calcium oxalate appears to precipitate with greater facility than does physiological mineral. Bone showed the features of mixed uraemic osteodystrophy in all four patients. We conclude that: (1) the fractures occurred through heavy crystal deposits; (2) ununited fractures and intra-osseous and subperiosteal tophi contributed to the pain; (3) spontaneous fractures are of poor prognostic significance. We recommend that unstable fractures be internally fixed.