Validation of the finding of hypertrophy of the clava in infantile neuroaxonal dystrophy/PLA2G6 by biometric analysis.

INTRODUCTION: Infantile neuroaxonal dystrophy (INAD), an autosomal recessive neurodegenerative disorder due to PLA2G6 mutation, is classified both as a PLA2G6-associated neurodegeneration (PLAN) disorder and as one of the neurodegeneration with brain iron accumulation (NBIA) disorders. Age of onset and clinical presentation in INAD is variable. Typically described imaging features of cerebellar atrophy, cerebellar cortex bright FLAIR signal, and globus pallidus iron deposition are variable or late findings. We characterize clinical and neuroimaging phenotypes in nine children with confirmed PLA2G6 mutations and show a useful imaging feature, clava hypertrophy, which may aid in earlier identification of patients. Measurements of the clava confirm actual enlargement, rather than apparent enlargement due to volume loss of the other brain stem structures. METHODS: A retrospective clinical and MRI review was performed. Brain stem measurements were performed and compared with age-matched controls. RESULTS: We identified nine patients, all with novel PLA2G6 gene mutations. MRI, available in eight, showed clava hypertrophy, regardless of age or the absence of other more typically described neuroimaging findings. Brain autopsy in our cohort confirmed prominent spheroid bodies in the clava nuclei. CONCLUSION: Clava hypertrophy is an important early imaging feature which may aid in indentification of children who would benefit from specific testing for PLA2G6 mutations.

Cell-mediated allergy to a cerebral aneurysm clip: case report.

BACKGROUND AND IMPORTANCE: Titanium aneurysm clips have superior imaging characteristics and have been supplanting their stainless steel counterparts. We report the case of a 36-year-old woman with a histologically demonstrated cell-mediated reaction to a cobalt alloy aneurysm clip. CLINICAL PRESENTATION: The patient underwent a craniotomy and clip placement for a ruptured cerebral aneurysm. Both the aneurysm clip and the wires used to fix the craniotomy were made of stainless steel (cobalt and nickel) alloys. Postoperatively, the patient was plagued by intense pruritus. INTERVENTION: Skin patch testing revealed a severe reaction to nickel and cobalt. Surgical removal of the aneurysm clip and wires resulted in the disappearance of the patient's symptoms. A histological analysis of the tissue adjacent to the clip and wires was consistent with Type IV delayed type hypersensitivity. CONCLUSION: Stainless steel surgical implants in the head can cause diffuse, severe pruritus in susceptible individuals. Although the role of the aneurysm clip, as opposed to the more superficial wires, in the genesis of the patient's symptoms is not certain, this case demonstrates that a cobalt alloy aneurysm clip can activate T cells and cause an immunological reaction in the central nervous system.

Metastatic meningioma detected in pleural fluid.

Meningiomas with both malignant cytologic features and clinical behavior are rare. A 39-yr-old man with recurrent meningioma developed a pleural effusion which, on cytologic examination, contained metastatic meningioma. The diagnosis was subsequently confirmed histologically and ultrastructurally. In conclusion, metastatic meningiomas can retain meningotheliomatous cytologic features which may allow a diagnosis to be made of clinically unanticipated tumor spread.

Immunoreactivity of human MAb BT32/A6 with neuroepithelial tumors.

The present study was undertaken to determine the pattern of immunoreactivity of BT32/A6, a human IgM monoclonal antibody (MAb), with the following histological panels: 1) 30 human and non-human cell lines, 2) 32 normal human tissues, and 3) 28 tumors of central neuroepithelial origin (16 astrocytic; 11 non-astrocytic). Antibody BT32/A6 recognizes a surface and cytoplasmic antigen present on a variety of human tumor cell lines including gliomas, melanomas, neuroblastomas, and a few sarcomas. The antigen is present (at least focally) on 15/16 astrocytic tumor tissue sections (94%), and in some cases, on close to 100% of cells. All malignant cell types, including small anaplastic cells, giant cells, gemistocytic cells, and cells forming pseudopalisades were labeled by MAb BT32/A6. Non-astrocytic neuroepithelial tumors did not stain appreciably with MAb BT32/A6. There was weak immunoreactivity in a small subset of normal human tissues of epithelial and lymphoid origin, with the exception of adrenal cortex, which exhibited weak to moderate staining. All normal tissues of neuroectodermal and mesenchymal origin were unreactive. In conclusion, MAb BT32/A6 appears to be unique in that it recognizes a highly-expressed astrocytic tumor-associated antigen that is present on both low and high grade tumors. This makes it a strong candidate for further studies aimed at establishing its usefulness in the treatment of human astrocytic tumors.

Primary cerebellar T-cell lymphoma with acquired immunodeficiency syndrome.

We report a 33-year-old man with the acquired immunodeficiency syndrome (AIDS) and a solitary T-cell lymphoma. Systemic sites of lymphomatous involvement could not be identified. Subtotal resection of the lesion with cranial irradiation resulted in a marked neurologic improvement. Our case suggests that T-cell lymphomas should be considered in the differential diagnosis of a solitary mass of the cerebellum in patients with AIDS and that aggressive therapy may be warranted.

Neuropathological changes in chronic adult hydrocephalus: cortical biopsies and autopsy findings.

BACKGROUND: The cortical changes resulting from chronic hydrocephalus in adults are not well defined. METHODS: Retrospective analysis of twenty-one patients (age 64-88 years) with a clinical diagnosis of "normal pressure hydrocephalus" who underwent cortical biopsy at the time of intracranial pressure monitoring or shunt insertion, and eight patients who were biopsied but not shunted. Eleven brains (age 26-92 years), seven from patients who could be considered to have "normal pressure hydrocephalus", were also examined following autopsy. Age- and sex-matched control brains with small ventricles and no history of dementia were compared to the hydrocephalic brains. Senile plaques and neurofibrillary tangles were assessed semiquantitatively and a non-parametric statistical analysis was employed. RESULTS: Five biopsies exhibited both senile plaques and rare neurofibrillary tangles, while two had only neurofibrillary tangles. Neurofibrillary tangles were more prevalent in hydrocephalic brains than in controls. There was no difference in the prevalence of senile plaques between the two groups. Grumose bodies in the substantia nigra were identified in five autopsy brains, a prevalence higher than in control brains. CONCLUSIONS: These pathological features are not specific for hydrocephalus; however, they suggest that long-standing ventriculomegaly is associated with degenerative brain changes in sites beyond the periventricular white matter. The presence of senile plaques in cortical biopsies from hydrocephalic patients does not appear to be a contraindication to shunting; however a prospective study in patients undergoing intracranial pressure monitoring would better address the issue.

Neurological outcome in a porcine model of descending thoracic aortic surgery. Left atrial-femoral artery bypass versus clamp/repair.

BACKGROUND AND PURPOSE: In a porcine model of thoracic aortic cross-clamping (AoXC), we compared the incidence and severity of paraplegia with two surgical techniques: left atrial-femoral artery (LA-FA) bypass (BP group; n = 9) and clamp/repair (CR group; n = 8). The descending thoracic aorta was clamped near its origin and distal to the third intercostal artery for 30 minutes. The intervening three intercostal arteries were ligated and divided. METHODS: All animals received methohexital anesthesia and were hyperventilated to a Paco2 of 28 to 32 mm Hg. Animals in the CR group received mannitol, and after AoXC, proximal hypertension was controlled with phlebotomy. In the BP group, proximal hypertension was controlled with LA-FA bypass using a centrifugal pump (Biomedicus 520C). Proximal mean arterial pressure, distal mean arterial pressure, central venous pressure, and cerebrospinal fluid pressure were measured; radioactive microspheres were injected at baseline, at AoXC + 5 minutes, at AoXC + 20 minutes, at AoXC off + 5 minutes, and after resuscitation. Neurological function was assessed at 24 hours. The animals were killed, and the spinal cord was removed to determine spinal cord blood flow. Histological cross sections of the lumbar spinal cord were stained with cresyl violet/acid fuchsin and then examined with light microscopy to determine the ratio of altered to total spinal cord neurons. RESULTS: Fifteen animals survived (one death in each group) and were assessed neurologically at 24 hours after AoXC. Despite better distal perfusion and lumbar spinal cord blood flow in the BP group, during AoXC, and at AoXC off + 5 minutes, there was no significant difference in the severity of spinal cord ischemic injury between groups as assessed neurologically by Tarlov score (P = .90, Mann-Whitney U test). As well, the ratio of altered to total lumbar spinal cord neurons did not differ between groups (P = .24). CONCLUSIONS: In this chronic porcine model, distal circulatory support with LA-FA bypass afforded better distal perfusion and improved lumbar spinal cord blood flow but did not influence the severity of spinal cord ischemic injury when compared with a clamp/repair technique.

In situ characterization of beta-amyloid in Alzheimer's diseased tissue by synchrotron Fourier transform infrared microspectroscopy.

We report the first evidence of the structure of beta-amyloid protein as it exists in situ within a slice of human Alzheimer's diseased brain tissue. Using a Fourier transform infrared microspectroscopic technique, areas of interest can be selected for spectral measurements with regions of potential contamination masked. In so doing, it is possible to obtain infrared spectra only of beta-amyloid and not the surrounding grey matter within which it lies. However, to obtain spectra of high-quality signal-to-noise ratio using a conventional infrared source, we were limited to aperture sizes between 24 microns x 24 microns to 50 microns x 50 microns. Markedly improved high-quality spectra were acquired with infrared radiation provided by a synchrotron light source (National Synchrotron Light Source, Brookhaven National Laboratories), using aperture sizes as small as 12 microns x 12 microns. This allowed spectroscopic mapping of brain tissue regions containing amyloid. We observe that in situ protein of grey matter exist predominantly in an alpha-helical and/or unordered conformation, whereas within amyloid deposits a beta-sheet structure predominates. The hydrogen bonding strength of the beta-structure found in situ is different from that reported in the literature for isolated/chemically synthesized beta-amyloid peptides.

Periodontoid synovial cyst causing cervico-medullary compression.

BACKGROUND: Periodontoid synovial cysts are rare lesions which may produce symptomatic cervico-medullary compression. METHOD: We report such a patient, whose progressive neurological deterioration required surgical treatment by transoral odontoidectomy and decompression. RESULTS: The diagnostic and theraputic interventions are described, including a lumbar puncture which precipitated a transient loss of consciousness and respiratory arrest. Surgery achieved clinical improvement, without complications or need for operative stablization. Detailed neuropathology is presented, as well as a literature review. CONCLUSION: Appropriate neuroradiological assessment is required in patients with suspected cervico-medullary compression, and symptomatic periodontoid synovial cysts may respond well to transoral surgical decompression.

Mobile lipid accumulation in necrotic tissue of high grade astrocytomas.

Multiple samples from 42 astrocytomas were investigated ex vivo by 1H MR spectroscopy followed by histological assessment. MR visible lipids were detected in 27 of 32 grade 4 astrocytomas. These lipids were heterogeneously distributed within the tumours. Their amount correlated positively with the amount of histologically detected necrosis. Mobile lipids were also observed in grade 4 astrocytoma samples without necrosis, as well as in one of three grade 3, two of three grade 2 and two of four grade 1 astrocytomas. The clinical significance of MR visible lipids, their cellular location, and their possible biological bases are discussed.

Neural network classification of infrared spectra of control and Alzheimer's diseased tissue.

Artificial neural network classification methods were applied to infrared spectra of histopathologically confirmed Alzheimer's diseased and control brain tissue. Principal component analysis was used as a preprocessing technique for some of these artificial neural networks while others were trained using the original spectra. The leave-one-out method was used for cross-validation and linear discriminant analysis was used as a performance benchmark. In the cases where principal components were used, the artificial neural networks consistently outperformed their linear discriminant counterparts; 100% versus 98% correct classifications, respectively, for the two class problem, and 90% versus 81% for a more complex five class problem. Using the original spectra, only one of the three selected artificial neural network architectures (a variation of the back-propagation algorithm using fuzzy encoding) produced results comparable to the best corresponding principal component cases: 98% and 85% correct classifications for the two and five class problems, respectively.

Beware of connective tissue proteins: assignment and implications of collagen absorptions in infrared spectra of human tissues.

Infrared spectra of human central nervous system tissue and human breast carcinoma are presented. The spectra are discussed in terms of the composition of the tissues. It is shown that differences between spectra of white and grey matter can be rationalised on the basis of differences in lipid content. Spectra of the choroid plexus and arachnoid villus of the meninges show a series of absorptions not observed in other CNS tissue. These absorptions are discussed in terms of the connective tissue content of the samples. We demonstrate that the presence of collagen results in the appearance of a series of characteristic absorptions which may be mis-assigned as DNA phosphate absorptions. The implications of the presence of collagen in tissues for the diagnosis of disease states by IR spectroscopic methods, with particular reference to cancer, is discussed.

Infrared spectroscopic characterisation of multiple sclerosis plaques in the human central nervous system.

Fourier transform infrared spectroscopy has been used for the characterisation of white matter, grey matter and multiple sclerosis plaques from human central nervous system tissue. We demonstrate significant differences in the infrared spectra of the three types of tissue, which show that an infrared spectroscopic discrimination of multiple sclerosis plaques from healthy brain tissue is possible in principle. The spectral changes reveal pronounced lipid loss in plaques, consistent with the demyelinating nature of the disease. The chronic plaques studied here can also be distinguished from other non-myelinated areas of the brain, based on differences in water content.

Paraplegia following thoracic aortic cross-clamping in dogs. No difference in neurological outcome with a barbiturate versus isoflurane.

BACKGROUND AND PURPOSE: We compared the incidence and severity of paraplegia following thoracic aortic cross-clamping in dogs for two anesthetic regimens. Animals were randomly assigned to receive methohexital (group M; n = 9) or isoflurane (group I; n = 9). We expected a better neurological outcome in animals administered methohexital because of superior neuronal protection and greater spinal cord perfusion pressure (mean arterial pressure below the cross-clamp site minus mean cerebrospinal fluid pressure). METHODS: After surgical preparation and a 30-minute stabilization period, dogs in group M received 14 +/- 6 mg.kg-1 i.v. methohexital to induce an isoelectric electroencephalogram followed by a continuous infusion of methohexital at 20 mg.kg-1 x h-1. Dogs in group I received 1.4 +/- 0.2% end-tidal isoflurane (1 minimum alveolar concentration). The thoracic aorta was then occluded 2.5 cm distal to the left subclavian artery for 30 minutes and then released. Hemodynamics and cerebrospinal fluid pressure were measured at (1) baseline, (2) 2 minutes after aortic cross-clamping, (3) 20 minutes after aortic cross-clamping, (4) 5 minutes after aortic unclamping, and (5) 30 minutes after resuscitation. At 24 hours a neurological assessment was performed. After the clinical assessment the dogs were killed and the spinal cord removed immediately for histopathologic study. RESULTS: There were no differences in nasopharyngeal temperature, PaCO2, pH, or hemoglobin at any time between groups. With cross-clamping, the spinal cord perfusion pressure decreased precipitously. However, there was no difference in spinal cord perfusion pressure between groups at any time (P = .5555). The neurological outcome, assessed at 24 hours after thoracic aortic cross-clamping by a veterinarian unaware of the anesthetic protocol, was not different between groups (P > .5, two-tailed Mann-Whitney rank-sums test). When anesthetized with methohexital 5 of 9 dogs were paraplegic; with isoflurane 7 of 9 dogs were paraplegic. By Spearman's rank test, a strong inverse correlation between the Tarlov score and the ratio of dead to total lumbar anterior spinal cord neurons was seen (Spearman's correlation coefficient = -.8358; P = .0001). CONCLUSIONS: We conclude that no advantage was offered by the choice of anesthesia to neurological outcome after 30 minutes of thoracic aortic cross-clamping in this canine model.

Use of neuroanesthesia adjuncts (hyperventilation and mannitol administration) improves neurological outcome after thoracic aortic cross-clamping in dogs.

BACKGROUND AND PURPOSE: Using a canine model of thoracic aortic cross-clamping, we compared the incidence and severity of paraplegia with and without standard neuroanesthesia adjuncts (mannitol administration and deliberate hyperventilation). Better outcome was predicted for animals treated with mannitol and hyperventilation. METHODS: Nineteen dogs (mean +/- SD weight, 21 +/- 3 kg) were anesthetized with methohexital to an isoelectric electroencephalogram. Animals were randomized to group C (control; n = 9) or group M (mannitol administration and deliberate hyperventilation; n = 10). In group C, animals were maintained normocapnic (PaCO2, 38 to 42 mm Hg). In group M, animals were hyperventilated to a PaCO2 of 28 to 32 mm Hg and received mannitol 2 g.kg-1 during surgical preparation, then 1 g.kg-1.h-1 by continuous infusion. The thoracic aorta was cross-clamped for 30 minutes. Systemic hemodynamics, cerebrospinal fluid pressure, and arterial blood gases were measured at (1) baseline, (2) 2 minutes after cross-clamp, (3) 20 minutes after cross-clamp, (4) 5 minutes after cross-clamp release, and (5) 30 minutes after resuscitation. No attempt was made to control the hemodynamic consequences of cross-clamping in either group. With release of the cross-clamp, PaCO2 was not controlled in group C; in group M the minute ventilation was further increased to maintain PaCO2 constant. At precisely 24 hours after cross-clamp the animals were assessed for incidence and severity of paraplegia, using the Tarlov score, by an observer unaware of the experimental protocol. The animals were killed, and the entire spinal cord was removed for histological assessment. Multiple sections of the lumbar spinal cord were processed and stained with hematoxylin and eosin. RESULTS: With application of the cross-clamp, cerebrospinal fluid pressure and central venous pressure increased significantly in both groups. However, in group M the maximal mean cerebrospinal fluid pressure never exceeded baseline values in group C. With cross-clamp release, spinal cord perfusion pressure (distal mean aortic pressure minus mean cerebrospinal fluid pressure) was significantly greater in group M (86 +/- 23 vs 65 +/- 17 mm Hg; P = .0017 between groups). Acid-base balance was better maintained in group M. The incidence and severity of paraplegia were significantly lower in group M (P = .043; Mann-Whitney rank-sums test, two-tailed). In this group 10 of 10 animals could walk and 4 of 10 had complete recovery. In group C 4 of 9 animals were paraplegic. There was a strong negative correlation between the Tarlov score and the ratio of dead to total anterior spinal cord neurons in the lumbar region as assessed by light microscopy (P = .0004; Spearman's rank test). CONCLUSIONS: We conclude that a protocol using standard neuroanesthesia adjuncts (mannitol administration and deliberate hyperventilation) is associated with improved neurological outcome after thoracic aortic cross-clamping of 30 minutes' duration in dogs anesthetized with methohexital.

Single-blind study of dystrophin staining in carriers of Duchenne muscular dystrophy.

A single-blind study of dystrophin staining in skeletal muscle was performed in 13 biopsies from carriers of Duchenne Muscular Dystrophy (DMD) and controls. The results indicate that immunohistochemical analysis of dystrophin staining is a valuable diagnostic test for DMD carriers when DNA for testing is unavailable from critical family members or is uninformative, when creatine kinase (CK) values are conflicting or when CK values must be used in isolation.

Hallervorden-Spatz disease: MR and pathologic findings.

PURPOSE: To compare the MR findings of eight cases with clinical diagnosis of Hallervorden-Spatz disease (HSD) with the pathologic findings of two other cases of HSD. MATERIALS AND METHODS: The eight imaged cases were studied with 0.5-T (seven cases) and/or 1.5-T (five cases) units. Six patients also had CT scans. The two other cases with proven HSD had detailed histologic evaluation. RESULTS: The 1.5-T findings showed abnormalities confined to the pallidum, which presented a diffuse low signal intensity in T2-weighted images, and an anteromedial area of high signal intensity (eye-of-the-tiger sign). In 0.5-T studies, low signal intensity was less evident and poorly detectable in spin echo, but gradient-echo images could enhance its demonstration; the area of high signal intensity was always well demonstrated. In three cases (three with 1.5 T, one with 0.5 T) a central spot of low signal intensity was seen in this area. The pathologic cases, in addition to neuroaxonal swellings and iron deposits, exhibited areas of "loose" tissue with vacuolization and lesser amounts of iron in the anteromedial part of the pallidum, in a location corresponding to the area of high signal intensity of the imaged cases. CONCLUSION: Comparison of MR findings with the pathologic studies demonstrates that the low signal intensity in T2-weighted images at 1.5 T corresponds to iron deposits in a dense tissue, and that the high signal intensity of the eye-of-the-tiger sign corresponds to an area of loose tissue with vacuolization. No correlation was found in the two pathologic cases for the central spot of low signal intensity.

Malignant astrocytoma of the optic nerve in a child.

Malignant gliomas of optic nerve and chiasm are rare, rapidly fatal neoplasms of adulthood. This report documents the occurrence of a malignant astrocytoma of the optic nerve in an 11-year-old boy who 9 years previously had a cerebellar medulloblastoma treated with surgery and irradiation. This malignant optic nerve glioma followed the same aggressive clinical course as that seen in adults, with death 9 months after diagnosis despite surgery and chemotherapy. Radiation may have been an important factor in the development of this malignant tumor which is almost never seen in the pediatric age group.

Persistent cerebrospinal fluid neutrophilia in delayed-onset neonatal encephalitis caused by herpes simplex virus type 2.

We describe an infant with three unusual features of perinatally acquired herpes simplex virus type 2 encephalitis: onset of illness at 34 days of age, absolute cerebrospinal fluid neutrophilia, and systemic viral dissemination after central nervous system disease. To provide early, effective antiviral therapy, clinicians should be aware of atypical presentations of serious herpes simplex virus infections.