Mitochondrial myopathy (complex I deficiency) associated with chronic intestinal pseudo-obstruction.

We report a patient presenting with severe muscular impairment and chronic intestinal pseudo-obstruction (CIP) at the age of eight months. Due to the aggravated symptoms, assisted ventilation, an ileostomy and total parenteral nutrition were required. Later on, the patient developed a locked-in syndrome (Leigh's subacute necrotising encephalomyelopathy) and finally died due to recurrent pneumonia and chronic renal failure. The assessment of muscle biopsies revealed a moderate single-fibre type II atrophy, a variation of muscle fibre calibre with focal fatty degeneration and a decreased reactivity of cytochrome-c oxidase. Although ragged red fibres had not been found, mitochondrial enzyme activities were markedly decreased with the lowest residual activity detected for NADH:Q1 oxidoreductase and NADH:O2 oxidoreductase (complex I deficiency), thereby confirming the diagnosis of mitochondrial myopathy. A molecular genetic analysis could not identify known mutations of mitochondrial DNA. Gastrointestinal full-thickness biopsies revealed myenteric hypoganglionosis of the colon and stomach and hyperplasia of the submucosal plexus of the ileum. Some of the intestinal smooth muscle cells displayed bulbous protrusions filled with lateralised mitochondria. Mitochondrial myopathies are known to be associated with a variety of clinical syndromes including CIP. However, in contrast to previous reports in which CIP has been attributed to visceral intestinal myopathies, the present case is characterised by neuronal intestinal malformations. Therefore, a mitochondrial myopathy associated with CIP requires a subtle assessment of both the intestinal smooth muscle and the enteric nervous system to identify the underlying pathology.

Procollagen I C-propeptide in the cerebrospinal fluid of neonates with posthaemorrhagic hydrocephalus.

BACKGROUND: The pathogenesis of posthaemorrhagic hydrocephalus (PHHC) following intraventricular haemorrhage (IVH) in premature infants includes a fibroproliferative reaction leading to arachnoidal fibrosis, ultimately causing malresorption of cerebrospinal fluid (CSF) at the arachnoid villi. AIMS: To determine whether an increased concentration of the carboxyterminal propeptide of type I procollagen (PICP) in the CSF of neonates after IVH reflects the activation of collagen synthesis preceding the manifestation of PHHC. METHODS: From 20 neonates with PHHC (median birth weight 740 g, median gestational age 25+1 weeks), 52 CSF samples were collected. CSF samples of four neonates (median birth weight 2170 g, median gestational age 32+4 weeks) with congenital non-haemorrhagic hydrocephalus served as controls. PICP was measured by radioimmunoassay. RESULTS: PICP in CSF taken at the start of external CSF drainage (median day 21, range 17-25 days postnatal age) was significantly increased (median 851.5, range 153.5-1944 microg/l) compared with controls (median 136.1, range 33.8-169.5 microg/l). CSF concentrations of PICP declined until permanent shunt placement (median day 70, range days 41-113). CONCLUSION: In neonates who develop PHHC, significant elevation of PICP concentration in the CSF is present 3-4 weeks after IVH. It reflects the increase of local type I collagen turnover, thereby correlating with manifestation of PHHC.

Improvement of oxygenation induced by aerosolized prostacyclin in a preterm infant with persistent pulmonary hypertension of the newborn.

OBJECTIVE: Case report on the effect of inhaled prostacyclin in a preterm infant (28 weeks gestational age) with respiratory distress syndrome complicated by marked hypoxemia due to persistent pulmonary hypertension of the newborn. Treatment with surfactant, hyperventilation, and elevation of systemic blood pressure had failed to improve oxygenation. MEASURES: A solution containing 10 micrograms PGI2/ml was aerosolized by the SPAG-2 aerosol-generator and then introduced into the afferent loop of the ventilatory circuit. RESULTS: Oxygenation improved dramatically and worsened when aerosolization was withdrawn. Intravenous prostacyclin had no additional effect on oxygenation. We observed no side effects on blood pressure and no bleeding complications. Inhalation was stopped after 40 hours and the baby was successfully weaned from the ventilator after 108 hours. CONCLUSION: Inhaled PGI2 had a beneficial effect on the oxygenation of a preterm neonate with persistent pulmonary hypertension of the newborn.

New horizons in neurology. The twentieth century.

Neurology in the twentieth century has undergone extraordinary change, particularly in the past 40 years. We trace the major trends, including the growth of the field, the technological advances, the revolution in neuroscience, the emergence of neurology as a free-standing specialty, the rise of child neurology, and the development of neurological subspecialization. Subsequent articles in this series will expand on these subjects.

Metabolic encephalopathy: neurologic and psychiatric considerations.

The diagnosis in patients who have psychiatric or neurologic manifestations as the result of toxins of great variety is not particularly difficult and usually can be achieved with a discerning history and physical examination. The EEG is a useful but not a necessary adjunct. The most difficult of these patients to sort out etiologically are those brought into the hospital, without history, in a flaccid coma or wild delirium or with mild or subtle delirium. The dementias are the main differential diagnosis. The hallmarks of metabolic encephalopathy are reduced awareness and fluctuating attention with defects in orientatioN, interpretation, memory, retention, and recall and with hesitant and clumsy motor performance. Prompt treatment is necessary to preserve the integrity of the master organ, the brain. Delay in treatment may convert metabolic encephalopathy into permanent dementia.