The persistent vegetative state.
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Humans↗
Biomedical subjects
D H Miller
Publications and source records attributed to D H Miller.
Differentiation of multiple system atrophy from idiopathic Parkinson's disease using proton magnetic resonance spectroscopy.
Proton magnetic resonance spectroscopy, localized to the lentiform nucleus, was carried out in 7 patients with the pure or predominantly striatonigral variant (SND) of multiple system atrophy (MSA), 5 patients with the olivopontocerebellar variant of MSA, 9 patients with a clinical diagnosis of idiopathic Parkinson's disease (IPD), and 9 healthy age-matched controls. The MSA group with predominantly striatonigral involvement showed a significant reduction in the N-acetylaspartate (NAA)/creatine ratio (median, 1.19; range, 0.96-2.0; p < 0.02) compared with the NAA/creatine ratio from the control group (median, 1.76; range, 1.61-2.0). In contrast, the IPD group had a normal NAA/creatine ratio (median, 1.82; range, 1.19-2.31; p > 0.05). The NAA/creatine ratio was markedly reduced in 6 of the SND patients and in only 1 IPD patient. The choline/creatine ratio was also significantly lower in the SND group (median, 1.02; range, 0.91-1.23; p < 0.04) compared with the control group (median, 1.22; range, 1.05-1.65). The IPD group showed a normal lentiform choline/creatine ratio (median, 1.13; range, 0.89-1.65; p = 0.25) compared with controls. The olivopontocerebellar group also showed a significant reduction in the NAA/creatine ratio from the lentiform nucleus (median, 1.47; range, 1.22-1.68; p < 0.01) compared with the controls as well as a nonsignificant reduction in the choline/creatine ratio (median, 0.93; range, 0.85-1.27; p < 0.4).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Cranial MRI in idiopathic retinal vasculitis.
Ten patients with clinically isolated idiopathic retinal vasculitis who had a positive family history for multiple sclerosis (MS) or positive typing for HLA B7 underwent magnetic resonance imaging (MRI) of brain and optic nerves in order to establish the frequency of clinically silent lesions. Brain MRI was normal in seven and abnormal in three: one had a single small white matter lesion, two had extensive white matter abnormalities resembling those seen in MS. In two patients a lesion was shown in the optic nerve. These findings suggest that a minority of patients with idiopathic retinal vasculitis have disseminated central nervous system lesions characteristic of MS, the frequency of such changes being less than in patients with isolated optic neuritis.
Adolescent↗
Magnetic resonance imaging and spectroscopy in multiple sclerosis.
Stimulated by the impressive effect of interferon beta on magnetic resonance imaging-detected disease activity, the past year or so has seen a particular interest in the use of magnetic resonance imaging to monitor treatment. To be effective in this regard, there needs to be a high sensitivity and accuracy in detecting disease activity, and the imaging findings should be predictive of clinical outcome, especially disability. A number of approaches show promise as being more sensitive than the conventional T2-weighted sequence. Furthermore, conventional magnetic resonance imaging cannot identify demyelination and axonal loss, the pathological substrates of irreversible disability. Newer magnetic resonance imaging techniques may be more pathologically specific, for example magnetization transfer imaging and magnetic resonance imaging spectroscopy. Such techniques provide new insights into the pathophysiology of multiple sclerosis. Improved methods for examining the often disabling spinal cord lesions have also emerged.
Aspartic Acid↗
Bilateral simultaneous optic neuropathy in adults: clinical, imaging, serological, and genetic studies.
To elucidate the cause(s) of acute or subacute bilateral simultaneous optic neuropathy (BSON) in adult life, a follow up study of 23 patients was performed with clinical assessment, brain MRI, HLA typing, and mitochondrial DNA analysis. The results of CSF electrophoresis were available from previous investigations in 11 patients. At follow up, five (22%) had developed clinically definite multiple sclerosis, four (17%) had mitochondrial DNA point mutations indicating a diagnosis of Leber's hereditary optic neuropathy (LHON). The remaining 14 patients (61%) still had clinically isolated BSON a mean of 50 months after the onset of visual symptoms: three of 14 (21%) had multiple MRI white matter lesions compatible with multiple sclerosis, three of 14 (21%) had the multiple sclerosis associated HLA-DR15/DQw6 haplotype, and one of seven tested had CSF oligoclonal IgG bands; in total only five (36%) had one or more of these risk factors. The low frequency of risk factors for the development of multiple sclerosis in these 14 patients suggests that few will develop multiple sclerosis with more prolonged follow up. It is concluded that: (a) about 20% of cases of BSON without affected relatives are due to LHON; (b) multiple sclerosis develops after BSON in at least 20% of cases, but the long term conversion rate is likely to be considerably less than the rate of over 70% seen after an episode of acute unilateral optic neuritis in adult life.
Adolescent↗
Progressive neuronal degeneration of childhood with liver disease (Alpers' disease) presenting in young adults.
Two unrelated and previously healthy girls, aged 17 and 18, presented with a subacute encephalopathy, visual and sensory symptoms and signs, and prominent seizures that were difficult to control. Brain MRI showed lesions (high signal on T2 weighted images) in the occipital lobes and thalamus; EEG showed slow wave activity with superimposed polyspikes. Inexorable downhill progression led to death in hepatic failure within eight months of onset. Histopathological findings in both patients ((a) chronic hepatitis with prominent bile duct proliferation, fatty change, and fibrosis; (b) in the brain a patchy destruction of the cerebral cortex, predominantly involving striate cortex) were characteristic of progressive neuronal degeneration of childhood with liver disease--Alpers-Huttenlocher syndrome--a rare autosomal recessive disorder usually seen in infants and young children.
Adolescent↗
High resolution magnetic resonance imaging of the anterior visual pathway in patients with optic neuropathies using fast spin echo and phased array local coils.
High resolution MRI of the anterior visual pathways was evaluated using frequency selective fat suppressed fast spin echo (FSE) sequences in conjunction with phased array local coils in patients with optic neuropathies. Fifteen normal controls and 57 patients were examined. Coronal T2 weighted fat suppressed FSE images were obtained in 11 minutes with an in plane resolution of 0.39 x 0.39 mm. The optic nerve and its sheath containing CSF were clearly differentiated. Central retinal vessels were often visible. In demyelinating optic neuritis and in anterior ischaemic optic neuropathy high signal within the nerve was readily delineated. Meningiomas and gliomas involving the optic nerve were precisely visualised both in the orbit and intracranially. Extrinsic compression of the optic nerves was readily visualised in carotid artery ectasia and dysthyroid eye disease. Enlarged subarachnoid spaces around the optic nerves were demonstrated in benign intracranial hypertension. High resolution MRI of the anterior visual pathway represents an advance in the diagnosis and management of patients presenting with optic neuropathy.
Adult↗
Signal intensity on MRI of basal ganglia in multiple sclerosis.
It has been reported that a relative reduction in signal intensity on T2 weighted MRI may be seen in the basal ganglia of patients with multiple sclerosis and furthermore that this is due to excessive iron deposition. The basal ganglia are, however, rarely involved clinically or pathologically in multiple sclerosis, casting some doubt on this finding. Therefore MRI was carried out in 46 patients with definite multiple sclerosis and 42 age matched controls. Contiguous, 5 mm thick axial dual echo spin-echo images of the brain were obtained on a 1.5T imager. Visual rating scales were used to measure the lesion load as well as the signal intensity of the globus pallidus, putamen, caudate nucleus, substantia nigra, red nucleus, and thalamus. There was a mild degree of low signal intensity in the patient group in the thalamus only. The signal intensity of the thalamus and putamen was never lower than that of the globus pallidus. Low signal in the basal ganglia is rarely, if ever, found in multiple sclerosis and is not a useful radiological sign.
Adolescent↗
Brain kallikrein-kinin system abnormalities in spontaneously hypertensive rats.
The objective of the present study was to determine whether the brain kallikrein-kinin system differs between spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) and if so, whether any detected differences occur before the development of hypertension in SHR. We measured cerebrospinal fluid levels of various components of the system in adult and young prehypertensive SHR and WKY. Cerebrospinal fluid kinin concentration and appearance rate were higher in SHR. Cerebrospinal fluid active kallikrein level and kininogenase activity were also higher in adult SHR. In addition, cerebrospinal fluid kinin concentration and appearance rate were higher in prehypertensive, 5- to 6-week-old SHR compared with age-matched WKY. However, no differences in cerebrospinal fluid kallikrein or kininogenase activity were observed between the two strains of young rats. Cerebrospinal fluid kinin concentration was higher in young versus adult rats of the same strain. In WKY, cerebrospinal fluid kallikrein also decreased with age although cerebrospinal fluid kallikrein concentration did not decrease in young and adult SHR. Together, these data suggest that there is a hyperactive kallikrein-kinin system in the brain of SHR that may contribute to the hypertensive state in this animal model.
Aging↗
Correlations between changes in disability and T2-weighted brain MRI activity in multiple sclerosis: a follow-up study.
We obtained two conventional unenhanced T2-weighted brain MRI scans, separated by an interval of 24 to 36 months, in 281 patients with multiple sclerosis (MS). At the time of each scan, clinical disability was rated using the Kurtzke Expanded Disability Status Scale (EDSS). Changes in disability between the two examinations correlated weakly but significantly with the number of new (Spearman's rank correlation coefficient = 0.13; p = 0.02) and enlarging (Spearman's rank correlation coefficient = 0.18; p = 0.002) MRI lesions. This result suggests that brain T2-weighted MRI is a useful supplementary marker of disease activity in definitive (phase III) clinical treatment trials in MS.
Adult↗
Management of mitochondrial disease on an intensive care unit.
Patients with mitochondrial disease may present to the Intensive Care Unit (ICU) with a variety of neurological and general medical disorders. Eleven patients were admitted to a neurological ICU between 1970 and 1992 because of respiratory insufficiency, status epilepticus and/or metabolic encephalopathy associated with mitochondrial disease. Respiratory impairment occurred in eight patients and was associated with nocturnal hypoventilation due to respiratory muscle weakness, aspiration due to bulbar weakness and abnormalities of central control leading to a reduced CO2 drive, irregular respiratory patterns and sleep apnoea. Seven patients received continuous respiratory support during the acute illness; three were subsequently weaned to domiciliary ventilation, and four died. Five patients had stroke-like episodes, which in two were recurrent. Four patients developed tonic-clonic grand mal epilepsy associated with myoclonic fits (2 patients), absences (2), focal fits (1) and status epilepticus (2). Encephalopathy was associated with recurrent lactic acidosis (2 patients), cardiac failure (2), hyponatraemia (2), renal abnormalities (3) and complete heart block (1). Although rare, mitochondrial disease should be considered in any patient with unexplained respiratory failure, intractable epilepsy, lactic acidosis or recurrent stroke.
Acidosis, Lactic↗
Management and outcome of severe Guillain-Barré syndrome.
Seventy-nine patients with Guillain-Barré syndrome admitted to a neurological intensive therapy unit (ITU) between 1985 and 1992 were studied retrospectively. The mean age was 49.8 years (range 16-86) and the time between the first neurological symptom and admission to ITU was 10.2 days (0-62). Admission was precipitated by a combination of respiratory failure requiring ventilatory support (73.4%), bulbar weakness (57.0%), autonomic features (11.4%) and general medical factors (10.1%). Specific treatments included plasma exchange (65.8%), intravenous immunoglobulin (13.9%) and methylprednisolone/placebo (12.7%). Significant complications included lower respiratory tract infections (45.6%), hyponatraemia (25.3%), dysautonomia (19.0%), urinary tract infection (12.7%) and cognitive disturbances (8.9%). Four patients (5.1%) died during the acute illness. Duration of nadir correlated with duration of ventilation, duration of ITU stay and outcomes at 3 months, 6 months and 1 year. However, time to nadir, an indicator of rapidity of deterioration, did not correlate with any outcome. The low mortality in this series of acutely ill and severely disabled patients suggests that specialized intensive therapy units continue to have an important role in the management of acutely ill patients with Guillain-Barré syndrome.
Acute Disease↗
Detection of multiple sclerosis by magnetic resonance imaging.
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Brain↗
Proton MRS in Huntington's disease.
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Brain↗
Are magnetic resonance findings predictive of clinical outcome in therapeutic trials in multiple sclerosis? The dilemma of interferon-beta.
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Clinical Trials as Topic↗
Correlation of magnetization transfer ratio with clinical disability in multiple sclerosis.
We performed spin echo magnetic resonance imaging with and without application of an off-resonance saturation pulse in 43 patients with multiple sclerosis (MS), 10 age-matched controls, and 4 elderly asymptomatic patients with the radiological diagnosis of small-vessel disease. Magnetization transfer (MT) ratio images were obtained from these. All MS subgroups (primary progressive, secondary progressive, benign, early relapsing-remitting) showed significantly lower average lesion MT ratios than small-vessel disease patients. Secondary progressive MS patients showed significantly lower lesion MT ratios than those with benign disease, and there was an inverse correlation of disability with average lesion MT ratio. The degree of reduction of MT ratios is an indicator of the extent of tissue destruction. Thus, reduced MT ratios in MS may provide an indication of the degree of demyelination and axonal loss, both of which are likely to cause functional deficits in MS. We conclude that MT measurement is (1) a robust quantitative method that may increase the pathological specificity of magnetic resonance imaging, (2) has the potential to differentiate demyelination in MS from less destructive pathological changes, and (3) may be useful in monitoring modifications in tissue structure brought about by treatment.
Adult↗
Magnetic resonance in monitoring the treatment of multiple sclerosis.
Magnetic resonance imaging (MRI) is increasingly being used as a measure of pathological disease activity in monitoring the efficacy of potential new treatments for multiple sclerosis. A major advantage of MRI over clinical monitoring is that it detects a large amount of subclinical disease activity. The two main approaches to MRI are detecting active lesions and measuring total lesion load. In relapsing-remitting and secondary-progressive multiple sclerosis, gadolinium enhancement increases the number of detectable active lesions and also probably correlates with pathological activity. Total brain-lesion load can be measured from computerized images, either by manual outlining of lesions or by more fully automated lesion-segmentation strategies. An important limitation of MRI monitoring is that conventional brain MRI abnormalities often show little or no relationship with clinical disability. One explanation for this may be pathological heterogeneity of lesions that all look the same on a conventional image. Other MR techniques are needed that specifically identify the pathological features most likely to result in disability, namely demyelination and axonal loss. Magnetization transfer imaging and proton MR spectroscopy are two techniques that show promise in this regard.
Brain↗
Dynamic gadolinium-enhanced MRI in the detection of spinal arteriovenous malformations.
Arteriovenous fistulae and malformations (AVFs and AVMs) of the spinal cord are rare, potentially treatable causes of progressive disability. Although a variety of MRI abnormalities has been described, the diagnosis rests on the findings on selective spinal angiography. Collecting T2*-weighted MR images during the passage of a gadolinium bolus gives information about perfusion and blood volume. We carried out dynamic MRI in seven patients with vascular abnormalities (5 dural AVFs, 1 intramedullary AVM, 1 cryptic angioma) and in two patients without an AVM. High resolution T1- and T2-weighted sagittal images of the whole spinal cord were first obtained using a multiarray receiver coil. Sagittal radiofrequency spoilt gradient echo images (GE34/25, flip angle 10 degrees) were then obtained during bolus injection of gadolinium-DTPA. Abnormalities were seen in all seven patients with AVFs or AVMs. In the patient with an intramedullary AVM and four of the five with dural AVFs transient signal reduction was seen within the perimedullary venous plexus during passage of the bolus. The findings correlated well with those from selective spinal angiography. We conclude that dynamic MRI offers a useful adjunct to angiography and may localise an arteriovenous shunt when conventional MRI fails to do so. In combination with high-resolution imaging of the entire spinal cord the technique may make myelography redundant; it is simple, well tolerated and can be carried out without significant time penalty.
Adult↗