Low plasma tryptophan in carcinoid patients is associated with increased urinary cortisol excretion

BACKGROUND: Previously we observed in patients suffering from a metastatic carcinoid tumor that irritability, aggression and lack of impulse control are associated with low levels of plasma tryptophan and presumably with low brain serotonin function. In rats we showed that a diet of low tryptophan resulted in higher stress responses and higher corticosterone production. Here we tested in carcinoid patients whether tryptophan depletion due to tumor 5-HT overproduction is associated with high cortisol production. METHODS: Urinary excretion of cortisol, serotonin, 5-hydroxyindole acetic acid (the main metabolite of serotonin a marker of tumor activity), plasma levels of tryptophan and platelet content of serotonin (index of peripheral serotonin synthesis) were determined in metastatic midgut carcinoid patients. Patients (N=25) were divided into two groups based on their plasma tryptophan levels (/=49mumol/l, n=13). RESULTS: Carcinoid patients with low plasma tryptophan levels had significantly higher urinary excretion of free cortisol (p<0.01), independent of tumor activity. The inter-individual differences in the low tryptophan group, however, were substantial. CONCLUSIONS: In a subgroup of the patients suffering from metastatic carcinoid disease the cerebral access of plasma tryptophan is impaired, thus rendering cerebral serotonin neurotransmission suboptimal and leading to hypercortisolism. The present study provides further support to the idea that low serotonergic function is a risk for developing stress-associated psychopathology.     

Recurrent acute necrotizing encephalopathy in a korean child: the first non-caucasian case

Acute necrotizing encephalopathy is characterized by fever, seizures, acute encephalopathy, and rapid progression to coma. It is usually associated with viral illness and shows characteristic brain magnetic resonance imaging features, including symmetrical involvement of bilateral thalami, brain stem, white matter, and cerebellum. After the first report of recurrent or familial cases in 2003, similar cases were found exclusively in American and European regions. The association with Ran-binding protein 2 gene was identified in 75% of familial or recurrent cases. This report describes a previous healthy 22-month-old boy who recurrently manifested typical clinical and radiological characteristics of acute necrotizing encephalopathy. His neurological outcome worsened with repeated episodes. There was no family history of acute necrotizing encephalopathy and no mutation in the coding region of Ran-binding protein 2 (RANBP2) gene. This is the first reported case of recurrent acute necrotizing encephalopathy in a non-Caucasian family.     

Subacute spongiform encephalopathy (Creutzfeldt-Jakob disease) with amyloid angiopathy.

A case is reported of Creutzfeldt-Jakob disease associated with amyloid infiltration of cerebral vessels. The duration of progressive dementia was only 4 months. Neuritic plaques were not a feature of the pathology. This report emphasises the association of spongiform encephalopathy with the presence of amyloid in the brain.     

Cerebral transmitter precursors and metabolites in advanced renal disease.

Patients with chronic renal disease had low plasma total tryptophan but an abnormally high proportion of this was in the free state. The subjects with encephalopathy had raised plasma free tryptophan, CSF tryptophan, and CSF 5-hydroxyindoleacetic acid. CSF tryptophan correlated better with plasma free than with plasma total tryptophan. Plasma and CSF tyrosine concentrations were normal but CSF homovanillic acid was raised especially in subjects with encephalopathy. The possible significance of these changes in advanced renal disease is discussed.     

Neurologic complications of carcinoid

We reviewed the records of all patients treated for carcinoid tumors at Memorial Sloan-Kettering Cancer Center from 1974 through 1984. Of 219 patients, 90 developed metastatic complications, and of these, 36 developed neurologic complications. Metastases, the most common neurologic complication, included epidural spinal cord compression (14 patients), intracranial metastases (13 patients), leptomeningeal metastases (1 patient), and peripheral nerve lesions (5 patients). Nonmetastatic complications were hepatic encephalopathy (six patients), herpes zoster infection (two patients), cerebral infarction due to septic emboli (one patient), superior sagittal sinus thrombosis (one patient), and carcinoid myopathy (one patient). The carcinoid syndrome was seen in eight patients (4%). Response of neurologic metastases to conventional radiation therapy was usually favorable. We conclude that (1) the frequency and type of neurologic complications associated with carcinoid tumors are similar to those seen with other systemic cancers; (2) CNS metastases are relatively common in patients with metastatic carcinoid (29%); and (3) the carcinoid syndrome is less common than CNS metastasis.     

Effect of dialysis on plasma and CSF tryptophan and CSF 5-hydroxyindoleacetic acid in advanced renal disease.

Patients with uraemic encephalopathy were previously found to have low total tryptophan (bound plus free), but high free tryptophan concentrations in the plasma and high CSF tryptophan concentrations. The 5-hydroxytryptamine metabolite 5-hydroxyindoleacetic acid was also raised in the CSF. A study of the effect of dialysis treatment on these substances in chronic uraemic patients with and without dialysis dementia is described. After an episode of dialysis the patients without dialysis dementia showed increased plasma total tryptophan and decreased free tryptophan. These changes were associated with a decrease of plasma free fatty acid. The patients with dialysis dementia did not show changes in tryptophan, but plasma free fatty acid rose. CSF concentrations of 5-hydroxyindoleacetic acid fell moderately in both groups of patients on dialysis.     

Rotavirus associated acute encephalitis/encephalopathy and concurrent cerebellitis: report of two cases

It is known that rotavirus gastroenteritis can accompany some neurological manifestations, including encephalitis/encephalopathy or seizures. However, the detailed pathogenesis involved has not been fully understood. To date, acute cerebellitis associated rotavirus gastroenteritis has not been previously reported, except for one case. Herein, we describe two cases of acute encephalitis/encephalopathy and concurrent cerebellitis, associated rotavirus gastroenteritis. Following vomiting and diarrhea, case 1 experienced convulsions and consciousness disturbance and case 2, transient loss of consciousness with eye deviation. After these symptoms subsided, cerebellar signs became evident and a brain MRI showed cerebellar involvement in both cases. Both cases showed speech disturbances, such as mutism, slow speech and dysarthria. In this report, we will discuss the possible pathogenesis of rotavirus associated acute encephalitis/encephalopathy and concurrent cerebellitis.     

Bronchogenic carcinoid metastasis to the intramedullary spinal cord

Carcinoid tumours are malignant tumours of neuroendocrine origin. Spinal-cord compression from carcinoid metastasis is uncommon, and intradural spinal carcinoid is rare. We report an instance of intramedullary carcinoid metastasis of the conus medullaris in the context of stable, asymptomatic systemic disease. To our knowledge this is the first reported case of intramedullary carcinoid metastasis.     

Non-convulsive status epilepticus of frontal origin as the first manifestation of Hashimoto's encephalopathy

Hashimoto's encephalopathy is an often misdiagnosed, life threatening, condition which improves promptly with steroid therapy. Since clinical manifestations are heterogeneous and non-specific, the diagnosis is often difficult. Several case reports of Hashimoto's encephalopathy presenting with partial or generalised seizures are described, but only a few have focused on status epilepticus as the first clinical manifestation. We report two patients presenting with repetitive and prolonged seizures characterised by progressive reduction in contact and reactivity associated with frontal/diffuse polyspike-and-wave activities. This condition, which can be interpreted as a form of non-convulsive status epilepticus (NCSE) of frontal origin, was refractory to antiepileptic drugs but responded promptly to high doses of intravenous steroid treatment. In cases of unexplained encephalopathy with EEG documentation of NCSE, the early recognition and treatment of Hashimoto's encephalopathy may lead to a favourable prognosis. [Published with video sequences].     

A case of autoimmune thyroid disease presenting posterior reversible encephalopathy syndrome

A 40-year-old woman was admitted to our hospital with disturbance of consciousness and seizure. We diagnosed encephalopathy associated with autoimmune thyroid disease (EAATD). Fluid-attenuated inversion recovery and diffusion-weighted MRI demonstrated hyperintense lesions in the left occipitotemporal lobe on admission, but these findings disappeared on day 11 without neurological deficits, compatible with posterior reversible encephalopathy syndrome (PRES). We report here this case of autoimmune thyroid disease presenting as PRES.     

Paralytic ileus in MELAS with phenotypic features of MNGIE

This report describes a child having the syndrome of overlapping phenotypic features of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE). Mitochondrial DNA analysis revealed a point mutation at position A3243G, whereas activity of thymidine phosphorylase and its corresponding gene analysis were normal. The most striking feature of this case was paralysis of one segment of the terminal ileum observed on laparotomy. The electron microscopic findings of the resected ileum and colon by limited right hemicolectomy disclosed accumulation of numerous enlarged mitochondria with ill-defined cristae which were similar to mitochondria reported in three previous MELAS cases and one MNGIE case with intestinal dysmotility. We emphasize that the MELAS and MNGIE phenotypes overlapped in this case and that the mechanism of acute ileus in MELAS was associated with functional paralysis of the intestine.     

Hashimoto encephalopathy responding to risperidone

This report describes a case of Hashimoto encephalopathy in an 11-year-old girl. She presented with features typical of this disorder including encephalopathy, seizures, and neuropsychiatric symptoms. Diagnosis was supported by an elevated thyroid-stimulating hormone level, a low levo-thyroxine level, and positive results for antithyroperoxidase antibody. Her response to typical treatment with levo-thyroxine was incomplete, requiring additional therapy with valproic acid and methylprednisone. Her course was further complicated by the development of acute psychosis. Treatment with risperidone was correlated with resolution of her psychosis and improvement in neuropsychiatric symptoms. Response to antipsychotic therapy has not previously been described in the pediatric population with Hashimoto encephalopathy. This case highlights the need for guidelines for the management of this rare disorder.     

Steroid-responsive encephalopathy associated with autoimmune thyroiditis and primary CNS demyelination

Steroid responsive encephalopathy associated with autoimmune thyroiditis is a well-recognized complication of autoimmune thyroid disease. However, the characterization of the histopathological features of steroid responsive encephalopathy associated with autoimmune thyroiditis are limited to six cases. Reported pathological features include vasculitis involving venules and arterioles, lymphocytic perivascular cuffs and microglial activation. We report a case of SREAT with biopsy proven (on two occasions) primary CNS demyelination and radiological evidence of steroid responsiveness, identifying primary CNS demyelination as a complication of autoimmune thyroid disease.     

Paraneoplastic neurological syndromes in patients with carcinoid

Background: Paraneoplastic neurological syndromes (PNS) are mainly associated with small‐cell lung cancer, gynaecological tumours and lymphomas. Few studies report the association of neurological syndromes with a carcinoid, the majority being a serotonin‐related myopathy. We report four patients with a PNS associated with carcinoid. Patients and results: The clinical syndromes were sensory neuropathy, limbic encephalitis, myelopathy and brain stem encephalitis. Two patients had antineuronal autoantibodies (one anti‐Hu, one anti‐Yo), one patient had antinuclear antibodies, and one patient had no autoantibodies. For two of the carcinoids, expression of HuD in the tumour could be demonstrated. Conclusion: This study demonstrates that carcinoids can also be associated with classical antineuronal antibody‐associated PNS.     

Status Epilepticus as Manifestation of Posterior Reversible Encephalopathy Syndrome in a Healthy Child

Posterior reversible encephalopathy syndrome is a recently described cliniconeuroradiological syndrome reported in children with several predisposing conditions such as transplantation, autoimmune, hematological, infectious, renal, and neoplastic diseases or administration of chemotherapeutic immunosuppressive drugs. Seizures are one of the most frequent manifestations of posterior reversible encephalopathy syndrome; status epilepticus has been described more frequently in adults but rarely in children. We report on the case of a 6-year-old healthy boy who presented status epilepticus as the main manifestation of posterior reversible encephalopathy syndrome in the absence of other underlying conditions. This is the first report of posterior reversible encephalopathy syndrome in a previously healthy child. Our case reminds us that pathogenesis of this condition is far from being completely understood and may include both genetic and environmental factors. Moreover, posterior reversible encephalopathy syndrome should always be suspected by clinicians in cases of status epilepticus with a prolonged neurological failure.     

Posterior reversible encephalopathy syndrome revealing acute post-streptococcal glomerulonephritis

A case of acute encephalopathy with posterior corticosubcortical vasogenic edema on magnetic resonance imaging is reported. Angiography showed cerebral arterial vasospasm. A diagnosis of acute post-streptococcal glomerulonephritis was made 2 days after admission. This report highlights the fact that acute post-streptococcal glomerulonephritis can be revealed by a posterior reversible encephalopathy syndrome and that cerebral vasospasm can concur with vasogenic edema in this condition.     

Acute and chronic progressive encephalopathy due to gasoline sniffing

Acute encephalopathy caused by gasoline sniffing is well recognized, but has been thought to be completely reversible. We report a patient who developed a progressive encephalopathy characterized by ataxia, tremor and dementia following repeated, deliberate gasoline inhalation. Blood and urine lead levels were consistently elevated and at autopsy, the formalin-fixed brain lead content was between 5200 and 6500 micrograms/100 gm of tissue. This case shows that repeated gasoline sniffing can result in irreversible encephalopathy and that both the acute and chronic encephalopathy probably result from organic lead intoxication and not from the gasoline itself.     

Severe dysautonomia revealing Wernicke's encephalopathy

Introduction

Wernicke's encephalopathy, a pathology caused by vitamin B1 (thiamin) deficiency, is often difficult to diagnose and can lead to severe cognitive sequels if left untreated.

Case report

We report the case of a 42-year-old HIV-positive women who, four days after recurrent episodes of vomiting, developed severe dysautonomia and symptoms suggestive of Wernicke's encephalopathy. Treatment with parenteral thiamine induced dramatic improvement within a few days.

Conclusion

This case report highlights an unusual presentation of symptomatic thiamin deficiency associating severe dysautonomia with the classical manifestations of Wernicke's encephalopathy. As dysautonomia is frequently the earliest sign of beriberi, this case illustrates the continuum between these two diseases whose cause, symptomatic thiamin deficiency, is the same. It also draws attention to the multiple risk factors that may be associated, leading to symptomatic thiamin deficiency. This deficiency, while often overlooked, is frequent in HIV-infected patients. Finally, this case contributes to the discussion on the possible genetic polymorphism that may make a limited deficiency symptomatic.     

A case of rhabdomyolysis associated with Salmonella encephalopathy

We report a case of severe rhabdomyolysis associated with Salmonella encephalopathy. A 3-year-old girl was admitted to our hospital because of status convulsives and unconsciousness. She was diagnosed as having Salmonella encephalopathy with rhabdmyolysis, and was treated by mild hypothermia and mechanical ventilation. Five days later she developed anuria with increased serum levels of myoglobin, CK and creatinine. And the diagnosis of acute renal failure was made. Peritoneal dialysis was begun from 6 days after admission. Hyperinfusion, the usual therapy of rhabdomyolysis, was not performed. She survived showing gradual improvement of renal function and consciousness. In a case of rhabdomyolysis complicating a neurologic disorder, a well-known poor prognostic factor, priority should be given to brain protection rather than to symptomatic treatment of rhabdomyolysis.     

Early infantile epileptic encephalopathy: a case associated with hemimegalencephaly.

The authors report a case of early infantile epileptic encephalopathy (EIEE) associated with hemimegalencephaly. The etiological factors in previously published cases of EIEE are reviewed and attention is focused on the high proportion of cases associated with neuronal migration disorders. We suggest that idiopathic cases of EIEE would be due to such disorders.