Gerstmann-Sträussler-Scheinker disease is an autosomal dominant prion disease. The clinical features include ataxia, dementia, spastic paraparesis and extrapyramidal signs.

We report a new large Italian family affected by Gerstmann-Sträussler-Scheinker disease.

The four generation pedigree includes 11 patients. The mean age at onset ± SD was 41.4 ± 16.2 years. Mean disease duration to death in four patients was 5.5 ± 1.7 years. Two clinical patterns were evident: cognitive impairment with scarce neurological features or ataxia followed by cognitive impairment. Molecular analysis showed P102L mutation in PRNP gene.

Three Italian families have been reported to date. The variable phenotype has already been reported, and does not appear related to the codon 129 polymorphism.

Several animal models of cerebral ischemia have been developed to investigate both pathophysiology and pharmacological treatment. The aim of this study was to verify the prognostic value of EEG power spectra analysis in a two-vessel plus hypotension rat model of transient global ischemia.

Spontaneously hypertensive rats (SHRs) and Wistar Kyoto rats (WKYs) were subjected to 20 min bilateral common carotid artery occlusion plus hypotension by sodium nitroprusside followed by reperfusion for seven days. Sham-operated animals served as controls. The changes after ischemia in EEG power spectra, and their relations with neuronal damage and astrocytic response were investigated.

The EEG analysis revealed that in SHRs and WKYs, ischemia produced a dramatic increase in delta activity and a decrease in theta, beta and alpha activities derived from both cortical and hippocampal areas. EEG activity reverted to normal values more quickly in WKYs than in SHRs which did not recover cortical and hippocampal alpha and beta activities even at six days of reperfusion. SHRs presented more severe damage and intense astrocytosis than WKYs in almost all the brain regions analyzed. In SHRs, hippocampal delta activity was positively correlated with the degree of neuronal necrosis and astrocytic activation, whereas theta, alpha and beta activities correlated negatively. No correlations were found in WKYs.

These data indicate that the hippocampal bioelectrical activity recorded in SHRs from the beginning of reperfusion could be useful for predicting the ischemic outcome and evaluating the effects of pharmacological interventions.

To report a case of disc herniation at Tl-2.

A 57-year-old man presented with hand weakness, Horner's syndrome, and pain radiating along the medial aspect of one upper extremity. Magnetic resonance imaging demonstrated extruded Tl-2 disc herniation with upward herniation of a sequestrated fragment.

An anterior approach was used to excise the disc, that was compressing the spinal cord and the Tl nerve root. All the patient's symptoms resolved completely, including Horner's syndrome.

Anterior discectomy may be the simplest and most effective method for disc excision and relief of spinal cord and Tl nerve root compression.

To describe a case of Pasteurella multocida meningitis associated with acute disseminated encephalomyelitis (ADEM).

A 33-year-old woman employed in a dog pound presented herself to hospital with fever and meningismus and was found to have culture positive Pasteurella multocida meningitis. Despite appropriate antibiotic treatment her clinical course was characterized by a persistent fever and worsening encephalopathy, which prompted further neurological investigation. Spinal fluid exam and serial MRI scans as well as her one-year clinical course were found to be compatible with ADEM.

Persistent fever and worsening encephalopathy in meningitis may indicate a para-infectious immune process such as ADEM, and may serve as indications for further neurological investigation.

The Consortium to Investigate Vascular Impairment of Cognition (CIVIC) is a Canadian, multi-centre, clinic-based prospective cohort study of patients with Vascular Cognitive Impairment (VCI). We report its organization and the impact of diagnostic criteria on the study of VCI.

Nine memory disability clinics enrolled patients and recorded their usual investigations and care. A case report form included all vascular dementia (VaD) individual criteria for each of four sets (National Institute of Neurological Disorders and Stroke (NINDS-AIREN), Alzheimer’s Disease Diagnostic Treatment Centers (ADDTC), the ICD-10 Classification of Mental and Behavioural Disorders (ICD-10), and the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV)) of consensus-based diagnostic criteria and for the Hachinski Ischemia Score (HIS). Investigators, having completed the case report form, were asked to make a clinical judgement about the cognitive diagnosis based on the best available information, including neuroimaging.

Of 1,347 patients (mean age 72 years; 56% women), 846 (63%) were diagnosed with dementia and 324 (24%) were diagnosed with VCI. The proportion of patients diagnosed with VaD by the diagnostic criteria was: 23.9% (n=322) by DSM-IV, 10.2% (n=137) by HIS, 4.3% (n=58) by ICD-10, 3.8% (n=51) by ADTCC, and 3.6% (n=48) by NINDS-AIREN. Judged against a clinical diagnosis of VaD, the sensitivity/specificity of each was: DSM-IV (0.77/0.80); HIS (0.41/0.92); ICD-10 (0.29/0.98); ADTCC (0.24/0.98); NINDS-AIREN (0.42/0.995). Compared with a clinical diagnosis of VCI, sensitivities were lower for the diagnostic criteria, reflecting the exclusion of patients who did not have dementia.

Consensus-based criteria for VaD omit patients who do not meet dementia criteria that are modeled on Alzheimer’s disease. Even for patients who do, the proportion identified with VaD varies widely. Criteria based on empirical analyses need to be developed and validated.

Cerebral aneurysms are the predominant cause of spontaneous subarachnoid hemorrhage (SAH). However, if an aneurysmal cause has been excluded, there remains but a short list of other potential etiologies. Cerebral neoplasms are clearly on this list but are most commonly meningiomas or metastatic lesions. This article details a case of a neoplasm that presented exclusively with SAH.

A 40-year-old male presented with a SAH with normal cerebral angiography. The initial magnetic resonance image revealed a lesion in the right insula thought to be resolving hemorrhage. Subsequent images, however, revealed the mass to be enlarging.

Craniotomy and resection of the lesion established a diagnosis of a malignant oligodendroglioma.

An affirmation is made that patients experiencing ’angiographically-negative’ SAH should undergo MRI, occasionally on a serial basis, to exclude other etiologies for hemorrhage, including neoplasia.

Inadequate preclinical testing (e.g., rodent studies) has been partly blamed for the failure of many cytoprotectants to effectively treat stroke in humans. For example, some drugs went to clinical trial without rigorous functional and histological assessment over long survival times. In this study, we characterized recent experimental practices in rodent cytoprotection experiments to determine whether the limitations of early studies have been rectified.

We identified 138 rodent cytoprotection studies published in several leading journals (Journal of Neuroscience, Stroke, Journal of Cerebral Blood Flow and Metabolism and Experimental Neurology) for 2000 - 2002 and compared these to those published in 1990. From each study we determined the ischemia model, age and sex of the animal, the histological and functional endpoints used, and the methodology used to assess intra- and postischemic temperature.

Ninety-eight percent of recent studies used young adult rodents and most used males. Most studies (60%) did not assess functional outcome and survival times were often ≤ 48 hr (66%) for focal ischemia and ≤ 7 days (80%) for global ischemia. Over 60% of the experiments relied solely upon rectal temperature during ischemia and only 32.6% of ischemia studies measured temperature after surgery. The 1990 data were similar.

Many investigators ignore the need to assess long-term functional and histological outcome and do not accurately represent clinical conditions of ischemia (e.g., use of aged animals). In addition, intra- and postischemic temperature measurement and control is frequently neglected or inadequately performed. Further clinical failures are likely.

Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset disorder characterized by progressive ptosis, dysphagia and proximal limb weakness. The autosomal dominant form of this disease is caused by short expansions of a (GCG)6 repeat to (GCG)8-13 in the PABPN1 gene. The mutations lead to the expansion of a polyalanine stretch from 10 to 12-17 alanines in the N-terminus of PABPN1. The mutated PABPN1 (mPABPN1) induces the formation of intranuclear filamentous inclusions that sequester poly(A) RNA and are associated with cell death.

Human fetal brain cDNA library was used to look for PABPN1 binding proteins using yeast two-hybrid screen. The protein interaction was confirmed by GST pull-down and co-immunoprecipitation assays. Oculopharyngeal muscular dystrophy cellular model and OPMD patient muscle tissue were used to check whether the PABPN1 binding proteins were involved in the formation of OPMD intranuclear inclusions.

We identify two PABPN1 interacting proteins, hnRNP A1 and hnRNP A/B. When co-expressed with mPABPN1 in COS-7 cells, predominantly nuclear protein hnRNP A1 and A/B co-localize with mPABPN1 in the insoluble intranuclear aggregates. Patient studies showed that hnRNP A1 is sequestered in OPMD nuclear inclusions.

The hnRNP proteins are involved in mRNA processing and mRNA nucleocytoplasmic export, sequestering of hnRNPs in OPMD intranuclear aggregates supports the view that OPMD intranuclear inclusions are “poly(A) RNA traps”, which would interfere with RNA export, and cause muscle cell death.

Stereotyped, repeated transient ischemic attacks manifesting as pure motor hemiparesis are most often attributed to ischemia of the internal capsule or ventral pons resulting from in situ disease of the small penetrating arteries.

We report a 61-year-old man presenting with recurrent episodes of left-sided weakness consistent with the lacunar syndrome of pure motor hemiparesis. Subsequent neuroimaging revealed infarction of the right ventral pons and a critical basilar artery stenosis as the inciting lesion. Despite maximal antithrombotic therapy, he continued to have repeated symptoms. Angioplasty and stenting were attempted but both failed due to plaque recoil and technical difficulties. After the procedure, the patient had no further ischemic episodes and remained symptom-free at two months.

This case illustrates the imprecise and discordant relationship between the mode of presentation of a stroke syndrome and its presumed pathophysiology. The lacunar syndrome of pure motor hemiparesis should be recognized by clinicians as a mode of stroke presentation due not only to small vessel disease, but also to large artery atherosclerotic disease such as basilar artery stenosis. Prompt institution of treatment can lead to a good clinical outcome.

The radiographic identification of pineal cysts has increased dramatically within the last two decades due to the advent of magnetic resonance imaging. Pineal cysts are often found incidentally with only a minority of these lesions ever becoming symptomatic and requiring treatment. Many theories attempting to explain the pathogenesis of these cysts exist.

We describe a case of a 12-year-old girl who presents with a pineal hemorrhage of unknown etiology with associated hydrocephalus.

Her hydrocephalus was initially treated with an external ventricular drain followed by a third ventriculostomy. She had no evidence of elevated beta human chorionic gonadotropin or alpha-fetoprotein within the serum or cerebrospinal fluid. Follow-up imaging at seven weeks revealed resolution of her hemorrhage, however, there was development of a progressive cystic lesion within the pineal region. In order to make a definitive tissue diagnosis, a supracerebellar infratentorial surgical approach with complete resection was performed. During the resection, brownish fluid was aspirated from the cyst and the cyst wall was removed. The pathological diagnosis was a pineal cyst.

Although cases have been described of pineal apoplexy with an underlying cyst, this case describes the development of a progressive pineal cyst secondary to a hemorrhage. This case demonstrates that pineal hemorrhage may be a promotor for the development or progression of pineal cysts.

Treadmill training is used for promoting rhythmical vigorous walking and for task-related training in patients with stroke. The neurological impact of treadmill training has not been established. The present investigation is aimed at (1) examining neurological changes over a four-week period after middle cerebral artery occlusion (MCAO) in rats and (2) assessing the impact of one-week, two-week and four-week treadmill training in MCAO rats.

Male Sprague-Dawley rats were subjected to 60-minute right MCAO. All rats were randomly assigned to one of seven groups. Infarct volume and neurological score were measured.

Rats sacrificed 24 hours post MCAO had the largest infarct volumes (171.4 ± 14.4 mm3) and the highest neurological score (median: 2, range: 1-3). We noted that without treadmill training, infarct sizes and neurological score diminished with time. Treadmill training for at least one week further reduced infarct volume and significantly improved neurologic function in MCAO rats.

Treadmill training after focal cerebral ischemia significantly improves neurological outcome in MCAO rats. Treadmill training may be beneficial for ischemic brain recovery.

Clinical-pathological study of the case of a woman with amentia from birth.

A 45-year-old woman was institutionalized since the age of two and showed no change in 43 years. She did not stand, walk, talk, use her hands or comprehend. She was placed in a chair each day. She lacked control of bladder and bowel. She showed no mental capability.

The brain weighed 1250 gm and was normally developed. There were two anoxic-ischemic regions of damage. The hippocampus showed extensive damage bilaterally and the cerebellum showed watershed infarction bilaterally.

A perinatal anoxic-ischemic episode is suspected. Hippocampal damage was the only finding that might explain the failure of mental and motor development. If this hypothesis is correct, the function of the human hippocampus is broader than currently accepted.

In Wilson's disease (WD), brain magnetic resonance images (MRI) show increased signal intensity in T2 weighted images in the lenticular nuclei, thalamus and brainstem, including the substantia nigra. A poor therapeutic response to levodopa in WD suggests the mechanism of a postsynaptic abnormality. However positron emission tomography studies show an involvement of the nigrostriatal presynaptic dopaminergic pathway.

We report the clinical manifestations in a case of WD with akinetic-rigid syndrome and initial hesitation. The brain MRI showed an increased signal intensity lesion in the substantia nigra region, in addition to basal ganglion and thalamic lesions. However, dopamine transporter (DAT) imaging with 99mTc-TRODAT-1 revealed a nonsignificantly increased DAT uptake, suggesting a normal presynaptic nigrostriatal dopaminergic terminal.

We suggest that significant heterogeneity can be found in WD patients and a normal presynaptic dopaminergic pathway may occur in some patients, even those with typical akinetic-rigid syndrome and evidence of substantia nigra involvement in the brain on MRI.

Meningiomas of the anterior cranial fossa frequently present with impaired visual function. Recognition of this entity in the differential diagnosis of painless, progressive, and asymmetric optic neuropathy is important since reversal of visual loss is possible given timely surgical excision of the tumour.

A 76-year-old man presented with no perception of light in his right eye and a reduced visual acuity of 20/60 in his left eye with a markedly constricted visual field. His visual deterioration had progressed over the previous three months and was not associated with headache. Ophthalmoscopy showed normal optic discs. MRI scanning showed a large frontal basal meningioma, which was subsequently resected.

The patient noticed an immediate improvement in his vision in his right eye. Visual acuity in his right eye improved to 20/50 at six weeks postoperatively and to 20/25 at five months, with corresponding improvement of the visual field.

Complete monocular blindness due to tumour compressing or distorting the anterior visual pathways does not preclude recovery following timely decompressive surgery, especially when the appearance of the optic disc is normal.

Although the benefits of radiotherapy for pituitary adenomas are well-documented, post-irradiation sarcomas of the sella are rarely seen, with only 20 cases (mainly of fibrosarcoma) reported in the medical literature.

We describe a case of post-irradiation sarcoma five years after surgery followed by external-beam irradiation for an extensive and locally invasive growth hormone-secreting tumor. The patient was subsequently given pegvisomant, an antagonist of growth hormone receptor, to control symptoms of growth hormone excess.

The patient underwent transsphenoidal resection of the recurrent tumor, followed by adjuvant chemotherapy. This led to significant relief in the patient's symptoms including radiological evidence of tumor shrinkage, but the tumor regrew when, owing to dose-limiting toxicity, chemotherapy was stopped.

Post-irradiation sarcomas of the pituitary are well-recognized but rare. They should be suspected in patients following sellar irradiation who show abrupt onset of new symptoms and appropriate radiological findings, and such tumors may respond to cytotoxic chemotherapy.