Hemorrhage due to tracheoarterial fistula with severe motor and intellectual disability.

BACKGROUND: Tracheoarterial fistula (TAF) is an unusual but highly lethal complication of tracheostomy, and successful surgical intervention for TAF has been reported. Few investigations are available for TAF in severe motor and intellectual disability (SMID). The aim of the present paper was to analyzed TAF in SMID to clarify which clinical variables might predict the occurrence of TAF, and adequate management for lifesaving. METHODS: Medical records at Metropolitan Fuchu Medical Center were retrospectively investigated for SMID between 1970 and 2000, and 10 TAF patients verified on operation or autopsy were identified. Details were reviewed including clinical status, emergency treatment at the occurrence of TAF, and operation and/or autopsy recordings. RESULTS: Four of 10 patients underwent successful operation and survived, while the other six died from hemorrhagic shock. Eight patients had tracheoinnominate artery fistula, the others had tracheocarotid artery fistula. Characteristic features as SMID such as etiology of brain disease, muscle tonus and convulsion were no apparent relevance to occurrence of TAF. All patients suffered from endotracheal granuloma extending to the arterial walls. Seven of 10 patients had re-bleeding after stabilization of the first massive hemorrhage, especially fiber bronchoscopy to confirm the diagnosis of TAF precipitated to fatal re-bleeding. One patient underwent interruption of the artery at relapse of TAF, the other three underwent suturing and had good outcome. CONCLUSIONS: There were no apparent predictors of TAF in SMID. Tracheal granuloma was recognized and consequent on formation of TAF, so control of granuloma may prevent TAF. Fiber bronchoscopy for suspected TAF is not recommended because it precipitates fatal bleeding.

Temporal lobe epilepsy caused by dermoid cyst.

A 15-year-old boy presented with a dermoid cyst in the left temporal lobe manifesting as complex partial seizures. Magnetic resonance imaging demonstrated a tumor with mixed signal intensity in the left anterior temporal subdural area, but no evidence of rupture. Intraoperatively, the tumor was located mainly in the deep sylvian fissure, adjacent to the amygdala, and had compressed the hippocampus. Intraoperative electrocorticography (ECoG) showed sporadic interictal spikes in both the adjacent areas of the tumor and over the anterior segment of the hippocampus. Total removal of the tumor and gliotic area of the surrounding tissue including the amygdala was performed. The hippocampal epileptic region was treated by transection of the pyramidal layer to preserve verbal memory function. Histological examination showed the dermoid tumor was closely attached to the brain parenchyma. The complex partial seizures ceased completely after surgery. Intraoperative recording of ECoG from the hippocampus and other limbic structures was very important to determine the epileptogenic area even if the tumor did not directly invade the hippocampus.

Brainstem and basal ganglia lesions in xeroderma pigmentosum group A.

Xeroderma pigmentosum group A (XPA) is a hereditary disorder characterized by cutaneous symptoms and progressive neurodegeneration. Since XPA patients exhibit peripheral neuropathy, neuronal deafness, rigidity, dysphagia, and laryngeal dystonia, it is indispensable for investigation of the neurodegeneration to analyze brainstem and basal ganglia lesions clinically and pathologically; we have previously shown the role of oxidative stress in the development of basal ganglia lesions. Here we immunohistochemically examined the expression of neurotransmitters, calcium-binding proteins, and neuropeptides in the brainstem, basal ganglia, and thalamus in 5 XPA autopsy cases. In the brainstem, immunoreactivity for tyrosine hydroxylase, tryptophan hydroxylase, and calbindin-D28K was severely reduced throughout the brainstem in all the XPA cases. Nevertheless, the expressions of parvalbumin, substance P, and methionine-enkephalin in the brainstem were comparatively preserved; the exception being reduced immunoreactivity for them in the cochlear and dorsal column nuclei in 3 cases. The large cell neurons in the putamen were preferentially reduced, the immunoreactivity for tyrosine hydroxylase reflecting the dopaminergic afferent and efferent pathways was severely affected, and the expression of 3 calcium binding proteins (i.e. parvalbumin, calbindin-D28K, and calretinin) was disturbed in various ways. The expression of substance P and methionine-enkephalin, which are involved in the efferent pathways in the basal ganglia, in the globus pallidus and substantia nigra was spared. It is speculated that the selective damage to the dopamine system in the basal ganglia and the disturbed monoaminergic expression in the brainstem could be related to clinical abnormalities such as the rigidity, laryngeal dystonia, and several neurophysiological changes. Functional analysis of autopsy brains will facilitate clarification of the pathogenesis of the neurodegeneration in XPA.

Clinical outcomes after corpus callosotomy in patients with bihemispheric malformations of cortical development.

OBJECT: Epilepsy in patients with bihemispheric malformations of cortical development (MCD) is typically medically intractable. Focal resection has been reported to be ineffective. Corpus callosotomy has been advocated as a treatment option, but the results have been reported only in several case reports. The authors describe a series of 10 patients with bihemispheric MCDs who underwent total corpus callosotomy. METHODS: The MCDs in these patients included lissencephaly, band heterotopia, perisylvian polymicrogyria, and tuberous sclerosis. Preoperatively all patients suffered disabling drop attacks or intense head drop seizures that caused frequent physical injuries. The follow-up period ranged from 1.4 to 5.8 years (median 3.2 years). Seizure outcome, parental assessment of daily function, and parental satisfaction with outcome were assessed postoperatively. Drop attacks disappeared completely during the entire follow-up period in eight patients and decreased to less than 10% of baseline in one. Other types of seizures were resolved completely in one patient and decreased in seven. Overall daily function improved and parents were satisfied with the surgery-related results in all patients except one who experienced a recurrence of drop attacks. There were no signs of significant and persistent neurological deficits in any case. CONCLUSIONS: Results of total corpus callosotomy in patients with bihemispheric MCDs were favorable in most cases. The procedure was particularly effective against drop attacks causing physical injuries and impaired quality of life in these patients.

Peculiar form of cerebral microdysgenesis characterized by white matter neurons with perineuronal and perivascular glial satellitosis: A study using a variety of human autopsied brains.

Microdysgenesis (MD) is a neuropathological term that implies a variety of minor developmental abnormalities of the brain. Recently, MD has been used for pathological diagnosis of cerebral tissues surgically resected from epileptic patients. However, criteria or consensus on pathological diagnosis of MD is still vague and controversial because of the lack of control studies. Therefore, this study paid special attention to the presence of white matter neurons with perineuronal glial satellitosis (WMN-GS) and perivascular glial satellitosis (PVGS) in the white matter, which are occasionally observed in epileptic foci, in order to clarify whether they could be handled as definite findings of MD. The materials included 80 autopsied whole brains ranging from normal subjects to patients with cerebrovascular disorder, neurodegenerative diseases and malformations. In each case, the presence of WMN-GS and/or PVGS was searched in 10 gyri in all five lobes (rostral frontal lobe, caudal frontal lobe, parietal lobe, temporal lobe and oc-cipital lobe) and evaluated. Statistically significant, WMN-GS and/or PVGS preferentially appeared in a diseased group consisting of neuronal migration disorder and related conditions, such as polymicrogyria, nodular heterotopia or tuberous sclerosis, leading to a suggestive conclusion that the presence of WMN-GS and/or PVGS could be a peculiar form of MD possibly derived from neuronal migrational arrest or related events, even if they appear alone without any other gross abnormalities.

Mutation analysis of the ALD gene in seven Japanese families with X-linked adrenoleukodystrophy.

The childhood cerebral form of X-linked adrenoleukodystrophy (X-ALD) is a severe congenital metabolic disease without a definite effective therapy except for hematopoietic stem cell transplantation in the appropriate disease stage. Seven Japanese families with X-ALD were analyzed for mutations in the ALD gene ( ALD). Of the seven families, three were referred to us for prenatal diagnosis, four for carrier detection, and three for confirmation diagnosis of patients. By nucleotide sequencing and/or restriction analysis, all the subjects to be examined were successfully diagnosed. Six different missense mutations in ALD were identified. There was a G-->A substitution (G512S) in two unrelated families, and a G-->A (R617H), a C-->T (R660W), a G-->C (R163P), a C-->T (S606L), or a G-->A (G116E) substitution in each of the other five families. Among the six substitutions, five were those reported previously and the other was a novel mutation. In three families, prenatal diagnosis was carried out after genetic counseling.

Oxidative stress and disturbed glutamate transport in spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a hereditary motor neuron disease, and three clinical subtypes of autosomal recessive SMA, including Werdnig Hoffmann disease (type 1), have been shown to be induced by deletion within the same genes. In order to clarify the pathogenesis of motor neuron degeneration in SMA, we immunohistochemically examine the expressions of oxidative stress-related materials (oxidative products) and glutamate transporters, which can prevent glutamate neurotoxicity, in five autopsy cases of SMA type 1. Age-matched controls did not show any deposition of oxidative products in the brain. In contrast, the abnormal deposition of 4-hydroxy-2-nonenal-modified protein, a product of membrane lipid oxidation, was observed in the spinal motor neurons in three cases, although the motor neurons did not show an increase of nitrotyrosine, which was observed in adult-onset amyotrophic lateral sclerosis. In addition, the nuclei of neurons and glial cells in the precentral gyrus, thalamus or cerebellar cortex were immunoreactive for 8-hydroxy-2'-deoxyguanosine in two cases, which was one of the most commonly used markers for oxidative DNA damage. Regarding glial glutamate transporters, three of five cases of SMA type 1 showed a reduction in immunoreactivity for excitatory amino acid transporter-1 (GLAST) in the ventrolateral nucleus of the thalamus, in which there was neither neuronal loss nor gliosis in routine histochemistry. One case, having mechanical ventilation, demonstrated a reduced expression of another glial glutamate transporter (GLT-1) throughout the central nervous system. These data suggest that oxidative stress and disturbed glutamate transport can partly be involved in the motor neuron devastation and/or latent thalamic degeneration in SMA type 1.

Postoperative development of children after hemispherotomy.

We studied the postoperative development of 14 children with cortical dysgenesis who underwent modified functional hemispherectomy (hemispherotomy) at the age of 6 years or younger. At follow-up of 24-72 months (median of 47 months), six (43%) were seizure-free, six achieved>90% reduction, one achieved 50-90% reduction, and one achieved 0-50% reduction in seizure frequency. At the preoperative and final postoperative examinations, mean scores of developmental quotient (DQ) were as follows: 25.5 and 31.9 in total DQ, 26.0 and 33.7 in intellectual DQ, and 27.4 and 22.9 in motor DQ. Children scoring >50 points in preoperative intellectual DQ score obtained near-normal intellectual DQ postoperatively, while, those scoring <10 DQ preoperatively remained at a low developmental level. Among children with DQ scores in the range from 10 to 50, two children who obtained seizure-free outcome and were operated upon in the first 3 years of life achieved marked developmental progress. The present study indicated that high preoperative intellectual DQ and cessation of seizures seem to be associated with better postoperative intellectual development. However, long-term observation of postoperative development and an accumulation of more cases will be needed before we can reach a firm conclusion.

Neurodegenerative mechanisms in subacute sclerosing panencephalitis.

Subacute sclerosing panencephalitis is caused by persistent brain infection of mutated measles virus, showing inflammation, neuronal loss, and demyelination. We neuropathologically examined six autopsy cases of subacute sclerosing panencephalitis, using in situ nick end-labeling and immunohistochemistry. Both the neurons and glial cells in the cerebral cortex showed immunoreactive nuclei in the nick end-labeling in two cases with disease duration within 2 years, whereas they were confined to the glial cells in the demyelinated cerebral white matter in three cases with disease duration ranging from 2 to 10 years. The nuclei and cytoplasm were immunoreactive for 8-hydroxy-2'-deoxyguanosine and 8-hydroxyguanosine, markers of oxidative damage to DNA and ribonucleic acid, respectively, in the cerebral cortex in three cases with disease duration within 9 years. In contrast, 4-hydroxy-2-nonenal-modified proteins, products of lipid peroxidation, were deposited in the demyelinated white matters in four cases with disease duration longer than 9 years. In three cases with long survival, the expression of glial glutamate transporters was reduced in the cerebral cortex. It is speculated in subacute sclerosing panencephalitis that apoptosis and oxidative stress to DNA can contribute to the early neuronal damage, whereas lipid peroxidation and disturbed glutamate transport may be related to the subsequent neurodegeneration.