Nonspecific White Matter Changes Research Articles

A case of chronic progressive Lyme encephalitis as a manifestation of late Lyme neuroborreliosis

A 54-year-old female living in Europe presented with gait ataxia, dizziness, and bilateral hearing loss. Magnetic resonance imaging (MRI) revealed non-specific white matter changes. The patient’s condition gradually deteriorated over two years without diagnosis. The patient continued to decline cognitively and neurologically with worsening ataxia and upper motor neuron signs. Repeat MRI showed worsening white matter changes. Lumbar puncture, not previously done, showed positive Lyme testing. Treatment with intravenous ceftriaxone resulted in marked neurological improvement. Four years after symptom, the patient has short-term memory deficits and chronic fatigue, but is otherwise neurologically, cognitively, and functionally intact. Follow up MRI findings remain largely unchanged. Because cases of intraparenchymal or encephalopathic neuroborreliosis in America are lacking, so are treatment options. We present a rare case and discuss our experience with antibiotic treatment. This case lends evidence to define optimal treatment of this disease, imperative for hastening neurological recovery.

P010 - Neuromyelitis optica: Case reports from Oman

Neuromyelitis optica (NMO), a multiple sclerosis mimic, is a rare disorder with a combination of optic neuritis and transverse myelitis. Only few cases were reported in Oman and were considered a diagnostic challenge. Most of them had an unusual presentation and were confused with multiple sclerosis. The neuromyelitis optica IgG test helped confirming the diagnosis. We present 4 cases of neuromyelitis optica from a tertiary referral hospital, Royal Hospital, Oman. The criterion of Wingerchuk et al. was used for the diagnosis. All patients had MRI brain and spine and neuromyelitis optica IgG test. First patient , a 29 years old female, was referred to outpatient clinic with a history of an attack of left optic neuritis. Subsequently had 3 recurrent attacks in Rt eye. After each attack she received IV methylprednisolone followed by a tapering dose of oral prednisolone. She had a partial recovery after each attack. Initial CSF oligoclonal bands and NMO IgG were −ve. MRI brain showed non-specific white matter changes. After the 4th attack of optic neuritis she was started on a monthly dose of cyclophosphamide. After the 7th dose she was changed to oral mycophenolate. After 9 months she had a new attack of optic neuritis and same treatment was continued. After 2 years free of relapses mycophenolate was stopped. After 4 months she developed acute paraplegia. MRI spine showed focal T2 hyperintensities from T3 to T5. Repeat NMO IgG was +ve. At this point a diagnosis of neuromyelitis optica was made and patient was planned for Rituximab therapy. Second patient is a 35 years old female, presented to neurology clinic with history of recurrent optic neuritis for which she was followed up by ophthalmologist. After 16 months she was admitted with acute transverse myelitis and optic neuritis. Initial NMO IgG was −ve. MRI brain showed nonspecific T2 hyperintensities. MRI spine showed diffuse T2 hyperintensties from C5 through T10. She was treated with IV methyl prednisolone, and because the response was not favorable, IV immunoglubulins was given, and maintained on prednisolone (tapering dose) and mycophenolate. On out patient follow up she continued to have mild residual weakness. After a year she developed another attack of paraplegia and optic neuritis; and was started on interferon. A repeat NMO IgG was +ve. After 2 months she developed another attack of paraplegia. And after 4 months it also recurred. She was offered treatment with Mitoxantrone but refused. Third patient is a 24 years old female, transferred to our hospital with 2 months H/O acute transverse myelitis and optic neuritis for which she was admitted to a local hospital and received IV methyl prednisolon. MRI brain showed multiple white matter T2 hyperintensities. MRI spine showed diffuse T2 hyperintensities C2 to T1 and T7–T12. Patient refused lumbar puncture. She was seen in neurology clinic after 2 months with 3 weeks H/O Lt optic neuritis and received IV methyl prednisolone. NMO IgG was +ve and was started on interferon. Seen again after 4 months. Doing well, ambulant without support. Patient lost to follow up. She subsequently deteriorated and was started on Rituximab. Fourth patient is a 46 years old female, admitted with urinary retention, generalized weakness, and altered sensorium. MRI brain : non-specific T2 white matter changes. MRI spine : extensive T2 hyperintensities from C2 to T1 and from T8 to T10 with contrast enhancement. Treated with methyl prednisolone. Had gradual progressive recovery. After 4 months had another attack of transverse myelitis. MRI spine : T2 hyperintensities from lower medulla to T10. Received IV methyl prednisolone. CSF oligoclonal bands was +ve. NMO IgG was +ve. ANCA-PR3 A6 was +ve. Cyclophosphamaide treatment was attempted but was not tolerated by patient and was stopped. Neuromyelitis optica should be suspected in any patient presenting with optic neuritis, transverse myelitis or both with an MRI brain not suggestive of multiple sclerosis. Neither a positive oligo clonal band in CSF, nor an initial negative NMO IgG test can exclude the diagnosis of NMO, as the former may be present in 35% of patients with NOM and the last can turn positive later on in the disease coarse. The diagnosis of NMO warrants early initiation of a disease specific therapy to prevent relapses.

Lyme disease: authentic imitator or wishful imitation?

Lyme disease: authentic imitator or wishful imitation?

Mucopolysaccharidosis type IVA: Evidence of primary and secondary central nervous system involvement

Mucopolysaccharidosis type IVA is a rare lysosomal storage disease caused by a deficiency of N-acetylgalactosamine 6-sulfatase. Studies usually focus on skeletal abnormalities and their consequences. This study explores the neurological manifestations in a cohort of mucopolysaccharidosis type IVA patients, with a detailed focus on brain and spinal magnetic resonance imaging (MRI) findings. We performed a cross-sectional study involving nine patients with a biochemical confirmation of mucopolysaccharidosis type IVA. The protocol consists of a comprehensive clinical examination and brain and spinal cord MRI analysis for all subjects. The mean age was 16.4 years (±5.7) and the mean onset of symptoms was 11.5 months (±6.3). Overall, cognition was spared in all but one patient and motor weakness was a constant finding in all patients. Deep sensation impairment was found in six patients. The brain MRIs showed non-specific white matter changes in two patients. Other abnormalities such as clival hypoplasia, basilar invagination, and arachnoid cists appeared in seven of the nine patients. Eight patients presented spinal cord compression, and in three of them, two spinal levels were compromised. Odontoid hypoplasia and degenerative features in the neuroaxis were present in all patients. Our experience with mucopolysaccharidosis type IVA patients supports the evidence of central nervous system involvement. We emphasize the importance of regular clinical assessments with complete MRI studies, as an attempt to detect the early signs of spinal cord compression. This evaluation may be especially important before surgical interventions, as occult lesions may become symptomatic and promote postoperative unfavorable outcomes.

Clinical Spectrum of Hereditary Spastic Paraplegia in Children: A study of 74 cases.

The aim of the study was to explore the spectrum of hereditary spastic paraplegia (HSP) in children in Oman. This retrospective study was carried out between January 1994 and August 2011 on children with delayed development, gait disorders and motor handicaps, with signs of symmetrical pyramidal tract involvement. A detailed perinatal and family history, including the age of onset of symptoms, was recorded. The children were labelled as having either the pure or complicated form of HSP based on the established diagnostic criteria. In families with more than one affected child, parents and all other siblings were also examined. Within the study, 74 children from 31 families were diagnosed with HSP. Parental consanguinity was seen in 91% of cases, with 44 children (59.4%) experiencing onset of the disease under one year of age. Complicated HSP was the most common type, seen in 81.1%. Speech involvement, mental retardation, and epilepsy were the most common associated abnormalities. Nonspecific white matter changes and corpus callosum abnormalities were noted in 24.3% of cases on magnetic resonance imaging. The study described clinical features of 74 children with HSP. Autosomal recessive complicated HSP was seen in 81.1% of cases.

Incidental White Matter Lesions in Children Presentıng With Headache

We aimed to describe the prevalence and significance of white matter lesions detected on magnetic resonance imaging (MRI) in children with headache. Children who were admitted with the complaint of headache and had neuroimaging between December 2007 and June 2012 were included in the study. The clinical and neuroimaging data of the patients were retrospectively evaluated. MRI results of the patients were documented in detail. The patients with non-specific white matter lesions were called for a control visit, and current status of headache and neurological findings were determined. A total of 941 patients were included in the study. Sixty-one percent of the patients received cranial neuroimaging. 8.2% had only cranial computed tomography (CT), 7.5% had cranial CT and cranial MRI, and 84.3% had only cranial MRI. 22.1% of the patients had abnormal cranial MRI findings. The rate of incidental non-specific white matter changes detected in our study group was 23/527 (4.4%). Among the 23 patients, 12 (52.2%) were male and 11 (47.8%) were female. Fourteen (60.9%) had migraine without aura, 8 (34.8%) had tension-type headache, and 1 (4.3%) had migraine with aura. Mean age of patients at the time of imaging was 12.1 ± 3.4 years (range 4.0-16.0 years). All patients with non-specific white matter changes on MRI showed normal psychomotor development, and there was no history of seizures or head trauma. The physical and neurological examinations of all patients were normal. The mean clinical follow-up period of the patients was 16.8 ± 17.3 months (range 6-80 months). No patients showed neurological deterioration during the follow up. The white matter lesions were supratentorial in all patients. The mean size of the lesions was 5.1 ± 4.5 mm (minimum, 2 mm; maximum, 24 mm). Repeated radiological evaluations were performed in 11 (47.8%) of the patients. No new white matter lesions were detected in control MRI during follow up. Non-specific incidental white matter changes may be seen in children with headache. For normal clinical follow up, in the absence of evident benefits from repeated imaging studies, we suggest that repeated imaging studies are not warranted in every patient and should be tailored according to clinical course.

Clinical and neuropathological features of X-linked spinal muscular atrophy (SMAX2) associated with a novel mutation in the UBA1 gene

Infantile-onset X-linked spinal muscular atrophy (SMAX2) is a rare lethal disorder linked to mutations in the UBA1 (previously UBE1) gene, encoding ubiquitin-activating enzyme 1 that has an important role in the ubiquitin-proteasome pathway. Published pathological reports are scarce. Here we report a male infant who presented from birth with predominantly truncal hypotonia following an antenatal history of reduced fetal movements. He had a myopathic face, profound weakness, multiple contractures and areflexia. Creatine kinase was moderately raised. Brain MRI showed non-specific symmetrical periventricular white matter changes. Neurophysiology revealed evidence of motor and sensory involvement and muscle biopsy showed marked inflammatory changes with subtle features suggestive of acute denervation. UBA1 sequencing revealed a novel hemizygous missense mutation (c.1670A>T; p.Glu557Val). He died from progressive respiratory failure at 4 months. On post mortem assessment, in addition to severe ventral motor neuron pathology, there was widespread involvement of the sensory system, as well as developmental and degenerative cerebellar abnormalities. In contrast to typical SMN1-associated SMA, the thalamus was unaffected. These findings indicate that SMAX2 is more accurately classified as a motor sensory neuronopathy rather than a pure anterior horn cell disorder. Ubiquitin-proteasome pathway defects may not only cause neurodegeneration but also affect normal neuronal development.

Neurosyphilis: MRI features and their phenotypic correlation in a cohort of 35 patients from a tertiary care university hospital

The clinical and MR imaging features of neurosyphilis are highly varied. In this study, we describe the spectrum of the imaging findings in patients with neurosyphilis. The MR imaging observations of 35 patients diagnosed to have neurosyphilis on the basis of cerebrospinal fluid reactive for the Venereal Disease Research Laboratory test were reviewed. All the 35 patients, including four with human immunodeficiency virus coinfection, met the CDC diagnostic criteria for neurosyphilis. Patients were classified into three groups: (1) neuropsychiatric, (2) meningovascular, and (3) myelopathic, based on the dominant clinical manifestations. Fourteen patients with neuropsychiatric manifestations showed diffuse cerebral atrophy (14), parenchymal signal changes in the mesial temporal region (2) and temporal and basifrontal regions (1), infarcts (3), and nonspecific white matter changes (3). Eleven patients with meningovascular form showed infarcts (6), diffuse cerebral atrophy (3), signal changes in the mesial temporal region (3), sulcal exudates (1), progressive multifocal leukoencephalopathy (1), and a mass surrounding the carotid sheath (1). Spine imaging in ten patients with myelopathy showed long-segment signal changes (5), contrast enhancement (2), and dorsal column involvement (2). Three of these patients had normal spinal study. Six patients in the myelopathic group also underwent brain MRI that showed signal changes in the temporal region (2) and frontal region (1), multiple infarcts (1), and enhancing hypothalami (1). Three patients had normal study. MRI abnormalities in neurosyphilis are protean and mimic of many other neurological disorders and thus require a high index of suspicion to reduce diagnostic omissions.

T2 Hyperintensity of Medial Lemniscus Is an Indicator of Small-Vessel Disease

Small-vessel disease is a common MRI finding that can be difficult to differentiate from other white matter (WM) diseases because of the lack of a specific pattern of brain involvement. The purpose of our study was to evaluate medial lemniscus hyperintensity seen on FLAIR images as an imaging marker for small-vessel disease. Two blinded neuroradiologists retrospectively reviewed 103 consecutive outpatient brain MRI studies. Medial lemniscus signal in the dorsal pons was evaluated visually on FLAIR images and after placing regions of interest (ROIs) on T2-weighted images. On the basis of the original interpretations, scans were divided into three categories: small-vessel disease, multiple sclerosis (MS), and normal or nonspecific WM changes. Cardiovascular risk factors were recorded. Analysis of variance and Fisher exact tests were used to determine group differences, and kappa statistics was used to determine interrater agreement. Thirty-seven patients had small-vessel disease, 14 patients had MS, and 52 had nonspecific WM changes. Medial lemniscus hyperintensity was seen in about 20% of patients with small-vessel disease and was generally bilateral. Although ROI analyses identified a slightly higher number of patients with medial lemniscus signal > 20% of adjacent to normal-appearing brainstem, interrater reliability was moderate, and there were false-positive and false-negative cases in comparison with visual data. When small-vessel disease patients were further subdivided into mild or advanced subgroups, medial lemniscus hyperintensity was selectively seen in advanced small-vessel disease. Patients with medial lemniscus hyperintensity were older (p < 0.001) and had higher prevalence of diabetes (p = 0.03), hypertension (p = 0.009), and hypercholesterolemia (p = 0.03). Medial lemniscus hyperintensity seen on FLAIR images is a reliable radiologic marker of advanced small-vessel disease.

Association of amyotrophic lateral sclerosis and Behcet’s disease: is there a relationship? A multi-national case series

Neurological involvement may be seen in 5-30% of the patients with Behcet's disease (BD). Occasionally, parenchymal neurological involvement in BD can present as a spinal cord syndrome. However, motor neuron disease-like presentation is extremely uncommon. Here we are reporting five patients (all male; median age, 38) fulfilling both International Study Group criteria for BD and El Escorial criteria for amyotrophic lateral sclerosis (ALS). These patients were identified by a questionnaire sent to the members of the Neuro-Behcet Study Group of the International Study Group for BD. Three out of five patients had only motor presentations. In two patients, sensory and urinary manifestations were present as well. Spinal cord MRIs were normal in all, and brain MRIs were normal in four patients; one patient had nonspecific white matter changes. Two patients passed away 1-3 years after diagnosis of ALS, and two patients were lost to follow-up 3 and 11 years after admission; one patient is still alive 3 years after onset. The patients that are presented here might represent a rare form of neurological involvement in BD as well as sole coincidence. Larger prospective series are needed to further answer this issue.

Neurological complications of pandemic influenza A H1N1 2009 infection: European case series and review

Neurological manifestations and outcomes of children with the 2009 H1N1 virus infection have been reported in three American series and from smaller cohorts and case reports worldwide. Of the 83 children admitted between April 2009 and March 2010 with H1N1 virus infection to a tertiary children’s hospital in a European setting, five children aged between 2 and 10 years had neurological symptoms. Four patients had seizures and encephalopathy at presentation. One patient presented with ataxia; one developed neuropsychiatric manifestations, and two developed movement disorders during the disease course. Early neuroimaging showed evidence of acute necrotising encephalopathy (ANE) in one case and non-specific white matter changes in another. Initial neuroimaging was normal for the other three, but interval MRI showed increased signal in bilateral periventricular distribution in one and significant cerebral volume loss in the other. Clinical outcomes varied: two recovered fully while three had residual seizures and/or significant cognitive deficits. Conclusion An analysis of our patients along with all reported cases reveal that seizures and encephalopathy were common neurological presentations associated with pandemic 2009 H1N1 influenza virus infection in children requiring hospital admission. Neuroimaging suggestive of ANE, basal ganglia involvement and volume loss appears to be associated with worse neurological outcome.

Deletion of 14-3-3ε and CRK: A Clinical Syndrome With Macrocephaly, Developmental Delay, and Generalized Epilepsy

Deletions of chromosome 17p13.3 result in neuronal migration defects such as isolated lissencephaly sequence and Miller-Dieker syndrome. LIS1 is the deleted gene within this region and is thought to directly cause isolated lissencephaly sequence and contribute to Miller-Dieker syndrome. Two additional genes (14-3-3ε and CRK) on the telomeric end of chromosome 17p reportedly contribute to the severe phenotype of Miller-Dieker syndrome. We report 2 patients with deletions of chromosome 17p13.3 involving the genes 14-3-3ε and CRK but not LIS1 with previously unreported, identical phenotypes of macrocephaly, small stature, dysmorphic features, generalized epilepsy, developmental delay, and nonspecific white matter changes. The findings in this report suggest that patients who have deletions of 14-3-3ε and/or CRK should be monitored closely for the development of seizures.

Non-Cardiac Manifestations of Neonatal Lupus Erythematosus

Neonatal lupus erythematosus (NLE) is characterized by the transplacental passage of maternal anti-Ro and/or anti-La antibodies and characteristic illnesses in the foetus/neonate. Most attention has focused on the most serious complication- cardiac involvement. This article will focus on non-cardiac involvement. Skin involvement (cutaneous NLE) is present in 15-25% of children with NLE. The rash of NLE tends to be photosensitive but may be present at birth or in non-sun exposed areas. It is most frequently seen around the eyes, not in the malar area, but also occurs in other parts of the body. The pathology resembles the rash of subacute cutaneous lupus erythematosus. Anti-Ro antibodies are present in >95% with the remaining mothers having anti-U1RNP antibodies only. Asymptomatic elevation of liver function tests, which may be associated with evidence of cholestasis, is seen in 10-25% of cases of NLE. Mild hepatomegaly and less commonly splenomegaly may be present. Liver involvement seen in isolation or associated with other features. The pathology resembles idiopathic neonatal giant cell hepatitis. Any haematological lineage, neutropenia and thrombocytopenia most commonly, may be affected by NLE. Haematological involvement is almost always asymptomatic. There are protean manifestations of neurologic involvement in NLE: hydrocephalus, non-specific white matter changes, calcification of the basal ganglia and a 'vasculopathy'. The most unusual feature of NLE is the radiographic finding of stippling of the epiphyses (chondrodysplasia punctata). Overall, non-cardiac involvement of NLE is more common than cardiac. The study of these manifestations may lead to new insight into how autoantibodies lead to disease.

Human herpesvirus-6 encephalitis following allogeneic hematopoietic stem cell transplantation

Immunosuppressive monoclonal antibodies directed to immune system cells may reduce rejection and graft versus host disease (GvHD) after allogeneic stem cell transplantation (SCT), but can increase the risks of viral infection. Here, we report human herpes virus-6 (HHV-6) encephalitis despite antiviral prophylaxis in 5 of 43 (11.6%) patients receiving alemtuzumab supported conditioning. Encephalitis occurred at 41-103 days (median 60 days) presenting with confusion in all patients, combined with amnesia (n=3) or seizures (n=2). MRI revealed non-specific white matter changes in two and a non-enhancing medial temporal lobe lesion in three patients. Cerebrospinal fluid (CSF) PCR amplification for HHV-6 was positive in all five patients, (600-2 25 000 (median 4700) copies/ml CSF), while analysis of peripheral blood revealed 100-22 500 (median 1200) viral copies/ml plasma. CSF protein was elevated in four patients, with minimal CSF pleocytosis. Intravenous foscarnet produced neurological improvement at 8-13 (median 11) days and negative plasma PCR at 30-66 (median 50) days. Four patients had complete neurological recovery, but one patient with persistent viral DNA in the CSF succumbed to progressive encephalopathy. Given this high incidence of HHV-6 and the possibility of successful outcome with prompt treatment, a high index of suspicion of this disorder is required in recipients of monoclonal antibody supported allografts.

The Importance of Liver Biopsy in the Investigation of Possible Mitochondrial Respiratory Chain Disease

The diagnosis of mitochondrial respiratory chain deficiency is usually made by analysis of mitochondrial respiratory chain activity in muscle biopsy. We describe 4 patients in whom the diagnosis was based on mitochondrial respiratory chain deficiency in liver alone. In 3 patients, liver complex IV activity was deficient, and the 4th patient had liver complex I deficiency (relative to citrate synthase and complex II activity). The enzyme activities in skeletal muscle biopsies from these patients were normal or equivocal. The age at presentation and the neurological symptoms differed from one patient to another. All 3 patients with complex IV deficiency had non-specific white matter changes on brain MRI. None of the patients had clinical or biochemical evidence of liver disease. These findings illustrate the wide variety of presentations associated with liver mitochondrial respiratory chain deficiency. They also demonstrate the importance of mitochondrial respiratory chain enzyme analysis in liver, in addition to muscle, even in cases where the primary clinical deficit is neurological and there is no liver disease.

Prognostic significance of white matter changes in a memory clinic population

Non-specific white matter changes (WMC) can be seen on neuroimaging of the brain in healthy elderly but are more common in dementia. WMC are correlated to specific cognitive deficits and might also contribute to global cognitive decline. The value of WMC as a predictor of cognitive impairment has been incompletely elucidated. We studied the prognostic significance of extensive WMC in a group of patients with memory disturbances, to evaluate if the presence of such changes predicts a poorer outcome. We retrospectively selected a group of 24 patients with prominent WMC on magnetic resonance imaging (MRI) and with different grades of memory impairment. We matched each patient, with regard to age, education, length of follow-up, initial score on the Mini Mental State Examination (MMSE) and initial diagnosis, to a patient without white matter pathology. The matched pairs were evaluated and the decrease in MMSE score after follow-up (range 2–4 years) was used as the outcome measure. Results showed no difference in the decrease in MMSE score at follow-up between patients with or without WMC. In conclusion, the presence of WMC in cognitively impaired patients had no effect on the progression rate of dementia, as measured by MMSE decline.

Magnetic resonance imaging in dementia: a study of brain white matter changes

Non-specific white matter changes (WMC) in the brain are common findings in the elderly population. Although they are frequently seen in non-demented persons, WMC seem to be more common in demented patients. The significance of these changes, as well as their pathophysiological background, is incompletely understood. The aim of this thesis was to study different aspects of WMC using MR imaging (MRI) and to investigate the clinical significance of such changes in subjects with mild cognitive impairment or dementia. In study I post-mortem MRI of the brain was compared to corresponding neuropathology slices. WMC were quantified and found to be more extensive on neuropathology. The areas that appeared normal on MRI but not on histopathology represented only minor changes with increased distance between the myelinated fibres but with preserved axonal network and glial cell density. Study II evaluated the blood-brain barrier (BBB) integrity to investigate if an increased permeability could be shown in WMC. A contrast-enhanced MRI technique was used to detect small degrees of enhancement. No general increase in BBB could be detected in the WMC areas. In study III the relation between WMC and apolipoprotein E (APOE) genotype was explored in patients with Alzheimer's disease (AD). Results showed that AD patients, who were homozygous for the APOE epsilon 4 allele had more WMC than patients with other genotypes. This was most significant for changes in the deep white matter. Results also indicated that in AD patients carrying the epsilon 4 allele, WMC are not age-related phenomena, but might be related to the aetiology of the disease. Study IV aimed to investigate if WMC in a specific brain region affect cognitive functions related to that area. Periventricular WMC in the left frontal lobe predicted a decrease in initial word fluency, a test though to reflect left frontal lobe functioning. This indicates that WMC might have specific effects in different brain regions. In study V we evaluated the prognostic significance of WMC in patients with memory impairment, regarding the rate of further global cognitive decline. There was no difference in outcome between patients having extensive WMC and a matched control group, during 2-4 years of follow up, and assessed by the "Mini-Mental State Examination". In conclusion, this work has shown and characterised pathological changes in the white matter not visible on conventional MRI. We have also shown that there is no major general increase in BBB permeability in areas of WMC. In addition, homozygosity with regard to the APOE epsilon 4 gene allele implies an increased extent of WMC in AD patients. In AD patients carrying this gene allele, WMC are not merely age-related phenomena, but might be related to the aetiology of the disease. We also claim that WMC in a specific location might impair cognitive functions that rely on those specific pathways. In contrast, WMC do not seem to have any prognostic value in predicting the rate of global cognitive decline in patients at a memory clinic.

Use of an intracranial near-infrared probe for localization during stereotactic surgery for movement disorders.

Localization of targets during stereotactic surgery is frequently accomplished by identification of the boundaries between the gray matter of various nuclei and the surrounding white matter. The authors describe an intracranial probe developed for this purpose, which uses near-infrared (NIR) light. The probe fits through standard stereotactic holders and emits light at its tip. The scattered light is detected and analyzed by a spectrometer, with the slope of the trailing portion of the reflectance curve used as the measurement value. Near-infrared readings were obtained during 27 neurosurgical procedures. The first three operations were temporal lobectomies, with values obtained from tracks in the resected specimen and resection bed. In the next five procedures, the probe was inserted stereotactically to a depth of 1 to 2 cm with measurements obtained every 1 mm. The probe was then used in 19 stereotactic procedures for movement disorders, obtaining measurements every 0.5 to 1 mm to target depths of 6 to 8 cm to interrogate subcortical structures. The NIR signals were correlated to distances beneath the cortical surface measured on postoperative computerized tomography or magnetic resonance imaging by using angle correction and three-dimensional reconstruction techniques. The NIR values for white and gray matter obtained during the lobectomies were significantly different (white matter 2.5+/-0.37, gray matter 0.82+/-0.23 mean +/- standard deviation). The NIR values from the superficial stereotactic tracks showed initial low values corresponding to cortical gray matter and high values corresponding to subcortical white matter. There was good correlation between the NIR signals and postoperative imaging in the 19 stereotactic cases. Dips due to adjacent sulci, a plateau of high signal due to subcortical white matter, a dip in the NIR signal during passage through the ventricle, dips due to the caudate nucleus, and peaks due to the white matter capsule between ventricle and thalamus were constant features. The putamen-capsule boundary and the lamina externa and interna of the globus pallidus could be distinguished in three cases. Elevated signals corresponding to the thalamic floor were seen in 10 cases. Nuances such as prior lesions and nonspecific white matter changes were also detected. There was no incidence of morbidity associated with use of the probe. Data acquisition was straightforward and the equipment required for the studies was inexpensive. The NIR probe described in this article seems to be able to detect gray-white matter boundaries around and within subcortical structures commonly encountered in stereotactic functional neurosurgery. This simple, inexpensive method deserves further study to establish its efficacy for stereotactic localization.

Repetitive and non-repetitive violent offending behaviour in male patients in a maximum security mental hospital--clinical and neuroimaging findings.

To examine if different violent offending behaviours are associated with different clinical and neuroimaging profiles. Thirty-nine schizophrenic and schizoaffective offenders from a maximum security mental hospital-20 repetitive violent offenders (RVOs) and 19 non-repetitive violent offenders (NRVOs)-were selected for clinical and neuroimaging assessments. Both groups had positive family history of mental illness and violence. Age, diagnosis, duration of illness, victim profiles and use of weapons at the time of the index offence were similar. RVOs had a higher prevalence of early parental separation, juvenile conduct problem, previous convictions of crimes not involving violence, impulsive suicide attempts, delusion of their lives being threatened at the time of the index offence and electroencephalographic (EEG) abnormalities localized to temporal lobes. NRVOs had a higher prevalence of sexual inexperience and command hallucinations to kill at the time of the index offence. Asymmetric gyral patterns at the temporo-parietal region were particularly common in RVOs and absent in NRVOs. Non-specific white matter changes in magnetic resonance imaging (MRI) and generalized cortical hypometabolism in positron emission tomography (PET) were present in both groups. Different structural and metabolic changes in the brain were associated with different violent offending behaviours. The complex interaction between violent behaviour, clinical features and neuroimaging findings in schizophrenia requires further studies.

Detection of tuberous sclerosis in parents by magnetic resonance imaging

We performed a detailed physical examination and MRI without gadolinium DTPA contrast in 60 couples with at least 1 child having tuberous sclerosis (TS). Eight parents had TS diagnosed by physical examination, family history, or various diagnostic procedures including MRI. Eight additional subjects and 6 control subjects had nonspecific high-signal white matter changes on MRI. MRI confirmed the diagnosis of TS in only 1 parent without physical findings of the disease, similar to the results of earlier studies using computed cranial tomography. CT may be less sensitive than MRI but is probably more specific for TS. Either CT or MRI may occasionally help substantiate the diagnosis of TS in a parent with few other findings. Both studies may need to be done in some parents to maximize the accuracy of genetic counseling.