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.

Mechanisms of neurodegeneration in mucopolysaccharidoses II and IIIB: analysis of human brain tissue.

Mucopolysaccharidoses (MPS) are inherited disorders caused by the deficiency of lysosomal enzymes. Sanfilippo syndrome (MPS III) and Hunter syndrome (MPS II) are characterized by severe and mild neurological disorders, respectively, in which the neurodegenerative mechanisms remain to be clarified. We immunohistochemically examined the involvement of tauopathy/synucleinopathy, cell death and oxidative damage in the brains of three cases each of MPS IIIB and MPS II and age-matched controls. In cases of MPS IIIB, the density of GABAergic interneurons in the cerebral cortex immunoreactive for calbindin-D28K and parvalbumin was markedly reduced when compared with age-matched controls. The swollen neurons showed immunoreactivity for phosphorylated alpha-synuclein but not for phosphorylated tau protein or beta-amyloid protein; those in the cerebral cortex demonstrated nuclear immunoreactivity for TUNEL, single-stranded DNA and 8-OHdG. Neither lipid peroxidation nor protein glycation was marked in MPS cases. The expression levels of superoxide dismutases (Cu/ZnSOD and MnSOD) and glial glutamate transporters (EAAT1 and EAAT2) were reduced in two MPS II cases. The disturbance of GABAergic interneurons can be related to mental disturbance, while synucleinopathy and/or DNA impairment may be implicated in the neurodegeneration of swelling neurons due to storage materials in MPS IIIB cases. These findings suggest the possibility of neuroprotective therapies other than enzyme replacement in MPS patients.

[Clinical characteristics of ulcerative colitis in four patients with severe motor and intellectual disabilities].

We retrospectively reviewed four patients with severe motor and intellectual disabilities (SMID), aged 8-56 years, who presented with ulcerative colitis (UC), and discussed causal interrelationships between UC and SMID. UC started at 3-50 years of age with early childhood-onset in two patients. Two patients had an intractable clinical course in which leukocytapheresis and surgery were ineffective, and resulted in steroid-dependency. We failed to find any causal relationships between infectious events, nutrition and anticonvulsants with the development of UC. However, when occult blood in feces is frequently positive in SMID patients, it is important to consider the possibility of UC and to perform an intestinal endoscopic examination.

An autopsy case of caudate nucleus lobulation accompanied with diaphragmatic eventration.

We describe an autopsy female case of multiple anomalies with lobulation of caudate nucleus tail, diaphragmatic eventration, skeletal anomalies, pyramidal tract anomaly, and meningothelial meningioma. Her psychomotor development was delayed, and she developed bilateral eventration of the diaphragms on X-ray film in her third decades. Right hemi-colonectomy was performed for volvulus at the age of 44 years, and meningioma was incidentally identified. She died at the age of 47 years. Autopsy demonstrated the partial deficiency of the muscular tissue in the circular thinned membranous area predominantly on left side including the central tendon of the diaphragm. The tails of the bilateral caudate nucleus demonstrated excessive lobulations, and the brainstem pyramidal tract showed hypoplasia. Immunoreactivity for tyrosine hydroxylase was deficient in the lobulated tail of caudate. We believe that this case is characterized by a rare combination of eventration, skeletal and nervous anomalies.

Pathological study of bronchospasms/tracheomalasia in patients with severe motor and intellectual disabilities.

This report concerns two autopsy cases of severe motor and intellectual disabilities (SMID) who died of bronchospasms or tracheomalasia. One case had no anatomical change in the tracheal wall except for an endotracheal granuloma, while the other showed softening of the tracheal wall. Since patients with SMID have risk factors for bronchospasms and tracheomalasia, such as gastro-esophageal reflux, aspiration, and thoracic deformities, it is important that we suspect the possibility of these conditions, when we see the respiratory distress in cases of SMID.

Laryngeal dystonia in a case of severe motor and intellectual disabilities due to Japanese encephalitis sequelae.

Laryngeal dystonia is characterized by stridor due to vocal cord dystonia and is observed in extrapyramidal disorders. Recently, botulinum toxin injection has been used as a primary therapy. Generally, severe motor and intellectual disabilities (SMID) are frequently complicated by various types of respiratory disorders. We report a SMID case with Japanese encephalitis sequelae showing repeated vocal cord abductor disturbance due to laryngeal dystonia, in addition to generalized dystonia, in whom MRI revealed basal ganglia lesions. Tracheostomy was effective for the case, and we believe that botulinum toxin injection may be inappropriate in SMID, both ethically and technically. Also, laryngeal dystonia should be considered as a cause of respiratory disorders in SMID.

Autopsy case of multiple anomalies with hypoplastic cerebrum, eyes, and endocrine organs, mimicking Micro syndrome.

We report an autopsy case of multiple anomalies with severe micrencephaly, bilateral microphthalmos, and hypoplastic endocrine organs. We examined expressions of calcium-binding proteins and hypothalamic and pituitary hormones. A female proband presented with microcephaly, microphthalmia, and psychomotor development delay. At the age of 23 years, she died of cardiorespiratory failure. The endocrine organs demonstrated severe underdevelopment, and the hypoplastic eyeballs had remnant lens, vitreous hemorrhage, and retinal detachment. The brain weighed 260 g; the cerebrum, cerebellum, and brain stem were extremely small; and the tertiary sulci were absent in the cerebral surface. The cross-sectional area of cerebral cortex was reduced to about one third of those in the control, although six-layered lamination, density of pyramidal neurons, and expressions of calcium-binding proteins were comparatively preserved in the cerebral cortex. The third ventricle was hypoplastic, and the bilateral thalami appeared to be fused and the hippocampus was unrolled, whereas the corpus callosum was preserved. In the hypothalamus, the paraventricular nucleus was only identified, and the adenohypophysial somatotrophs were reduced. This may be the first autopsy report of Micro syndrome, which is characterized by microcephaly, brain malformations, optic atrophy, and hypogenitalism, although the case lacked agenesis of the corpus callosum.

[A case of acute encephalitis with refractory, repetitive partial seizures (AERRPS) showing transient disappearance of the seizure with occurrence of choreo-ballistic movement].

We present here a 5-year-old girl with acute encephalities with refractory, repetitive partial seizures (AERRPS), a new clinical entity defined by the following five criteria: 1. acute encephalitis with a prolonged acute phase of more than 2 weeks, 2. persistent partial seizures with identical phenotype both in the acute and recovery phase, 3. seizures frequently evolving into convulsive status especially during the acute phase, 4. extremely intractable, and 5. no causative lesion or agent is identified. Interestingly, her seizures had completely diminished from the fifty-sixth day of her illness with concomitant appearance of choreo-ballistic involuntary movements. After the 120th day of the illness, seizures evolved again, though the involuntary movements persisted. This transient disappearance of intractable seizures might provide a clue to the pathophysiology of seizures in AERRPS.