Progressive extrapyramidal disorder with primary hypogonadism and alopecia in sibs: A new syndrome?

We report on 2 sibs with consanguineous parents, and an identical progressive extrapyramidal movement disorder with onset in adolescence and associated with progressive alopecia and primary hypogonadism. To our knowledge, this syndrome has not been reported, and probably represents a newly recognized autosomal recessive condition. © 1996 Wiley-Liss, Inc.     

Metastatic medullary thyroid carcinoma or calcitonin‐secreting carcinoid tumor of lung? A diagnostic dilemma in a patient with lung mass and thyroid nodule

Calcitonin‐secreting neuroendocrine tumors are rare and have been reported in literature as case reports or case series in various organs including lung, pancreas, larynx, bladder, and ovary. These tumors have similar cytologic features and immunohistochemical profile to medullary thyroid carcinoma and thus it is difficult to distinguish them, especially when calcitonin‐secreting neuroendocrine tumors are intermediate or higher grade and there is a mass lesion in the thyroid gland. Here, we report a rare case of calcitonin secreting atypical carcinoid tumor of the lung in a patient with thyroid nodule. However, after extensive ancillary studies on the thyroid gland, no tumor was detected and subsequent resection specimen revealed a pulmonary atypical carcinoid tumor with metastasis to level 11 lymph node. Being aware of this entity has significant clinical, diagnostic, and therapeutic implications and can prevent unnecessary thyroidectomies with subsequent possible morbidities.     

Choroidal abnormalities in café‐au‐lait syndromes: a new differential diagnostic tool?

The best known café‐au‐lait syndrome is neurofibromatosis type 1 (NF1). Legius syndrome (LS) is another, rarer syndrome with café‐au‐lait macules (CALMs). In young patients their clinical picture is often indistinguishable. We investigated the presence of choroidal abnormalities in syndromes with CALMs as a candidate tool for a more efficient diagnosis. Thirty‐four patients with NF1 (14 with a truncating mutation, 14 with a non‐truncating mutation and 6 with unknown mutation) and 11 patients with LS. All patients underwent an ophthalmological examination. Infrared images were performed. Choroidal nodules were diagnosed in 65% of the NF1 group. About 71% of NF1 patients with a truncating mutation and 50% of patients with a non‐truncating mutation were found to have nodules. Choroidal nodules were seen in 18% of the LS patients, never more than one nodule/eye was detected in this group. Choroidal nodules are more abundantly present in NF1 genotypes with truncating mutations. In contrast, the number of choroidal nodules in LS is comparable with their presence in healthy individuals. Especially at an early age, when the clinical picture is incomplete, the detection of choroidal nodules is of diagnostic value, and helps in an appropriate genetic counselling and follow‐up. These results support the suggestion to include choroidal nodules to the diagnostic criteria for NF1.     

Sinonasal haemangiopericytoma‐like tumour: a sinonasal glomus tumour or a haemangiopericytoma?

AIMS: Sinonasal haemangiopericytoma-like tumour is controversial with regard to its nosologic nature. This study aims to investigate its relationship with glomus tumour and haemangiopericytoma. METHODS AND RESULTS: Six cases of sinonasal haemangiopericytoma-like tumours identified in our files were reviewed for clinicopathological features, and compared with five cases each of soft tissue glomus tumour and meningeal haemangiopericytoma. Immunohistochemical studies for muscle-specific actin, smooth muscle actin, desmin and CD34 were performed. Sinonasal haemangiopericytoma-like tumour demonstrated a uniform histological appearance with bland-looking short, spindly cells forming sheets and short fascicles. The tumour cells were interspersed with slit-like, round and ectatic blood vessels. Actin immunoreactivity was demonstrated in all six cases, although occasionally patchy. The histological appearance and immunohistochemical phenotype of sinonasal haemangiopericytoma-like tumour were very similar to and focally indistinguishable from glomus tumour. Meningeal haemangiopericytoma, in contrast, was characterized by high tumour cellularity, random nuclear orientation, presence of staghorn vasculature and lack of immunohistochemical evidence of myogenic differentiation. CONCLUSIONS: We conclude that sinonasal haemangiopericytoma-like tumour is biologically close to or identical to glomus tumour, but is not related to haemangiopericytoma.     

NMR‐based metabolomic analysis of cerebrospinal fluid and serum in neurological diseases – a diagnostic tool?

We sought to evaluate the diagnostic accuracy of metabolomic biomarker profiles in neurological conditions (idiopathic intracranial hypertension (IIH), multiple sclerosis (MS) and cerebrovascular disease (CVD) compared to controls with either no neurological disease or mixed neurological diseases). Spectra of CSF (n = 87) and serum (n = 72) were acquired using ¹H NMR spectroscopy. Multivariate pattern recognition analysis was used to identify disease‐specific metabolite biomarker profiles. The metabolite profiles were then used to predict the diagnosis of a second cohort of patients (n = 25). CSF metabolite profiles were able to predict diagnosis with a sensitivity and specificity of 80% for both IIH and MS. The CVD serum metabolite profile was 75% sensitive and specific. On analysing the second patient cohort, the established metabolite biomarker profiles generated from the first cohort showed moderate ability to segregate patients with IIH and MS (sensitivity:specificity of 63:75% and 67:75%, respectively). These findings suggest that NMR spectroscopic metabolic profiling of CSF and serum can identify differences between IIH, MS, CVD and mixed neurological diseases. Metabolomics may, therefore, have the potential to be developed into a clinically useful diagnostic tool. The identification of disease‐unique metabolites may also impart information on disease pathology. Copyright © 2009 John Wiley & Sons, Ltd.     

Astrocytes and NG2‐glia: what's in a name?

Classic studies recognize two functionally segregated macroglial cell types in the central nervous system (CNS), namely astrocytes and oligodendrocytes. A third macroglial cell type has now been identified by its specific expression of the NG2 chondroitin sulphate proteoglycan (NG2-glia). These NG2-glia exist abundantly in both grey and white matter of the mature CNS and are almost as numerous as astrocytes. It is well established that NG2-glia give rise to oligodendrocytes. However, the majority of NG2-glia in the adult CNS proliferate very slowly and are non-motile. Both astrocytes and NG2-glia display a stellate morphology and express ion channels and receptors to neurotransmitters used by neurons. Both types of glia make intimate contacts with neurons in grey and white matter, and their functional differences and similarities are only beginning to be unravelled. Recent observations emphasize the need to examine the relationship between astrocytes and NG2-glia, and address the question of whether they represent overlapping or two distinct glial cell populations. To be of any relevance, this classification must relate to specific functions in the neural network. At present, the balance of evidence is that NG2-glia and astrocytes are functionally segregated populations.     

Attention deficit hyperactivity disorder with bipolar disorder in girls: further evidence for a familial subtype?

BACKGROUND: To clarify the nosologic status of girls with attention deficit hyperactivity disorder (ADHD) who also satisfy diagnostic criteria for bipolar disorder (BPD). METHODS: Using blind raters and structured psychiatric interviews, we examined 140 girls with ADHD, 122 non-ADHD comparisons and their 786 first degree relatives. Analyses tested specific hypotheses about the familial relationship between ADHD and bipolar disorder in girls. RESULTS: After stratifying our ADHD sample into those with and without BPD, we found that: (1) relatives of both ADHD subgroups were at significantly greater risk for ADHD than relatives of non-ADHD controls, (2) the two subgroups did not significantly differ in their relatives' risk for ADHD; (3) an elevated risk for bipolar disorder was observed among relatives when the proband child had BPD but not ADHD alone; (4) weak evidence of cosegregation between ADHD and BPD, and (5) no evidence of a trend for random mating between ADHD parents and those with mania. LIMITATIONS: Limitations of this study include the lack of direct interviewing of probands and the limited number of ADHD/BPD probands available. CONCLUSIONS: These findings extend to girls what was previously documented in boys and suggest that comorbid ADHD with BPD in girls is familially distinct from other forms of ADHD and may be related to what others have termed childhood onset BPD. Future work could determine if this subgroup has a characteristic course, outcome and response to treatment.     

Duct‐obstructive pancreatitis with granulocytic epithelial lesion in a patient with ulcerative colitis: An atypical manifestation of type 2 autoimmune pancreatitis?

Type 2 autoimmune pancreatitis (AIP) typically presents with diffuse or focal enlargement of the pancreas; however, its diverse clinical presentation has not yet been clarified. We herein described a 46‐year‐old man with a 1‐month history of ulcerative colitis who presented with imaging features of a mass‐like lesion in the pancreatic body with upstream duct dilatation and serum CA19‐9 elevation. He underwent laparoscopic distal pancreatectomy with splenectomy for suspected malignancy. Histologically, the area radiologically suspected to be duct dilatation consisted of necrotic tissue, in which the disrupted main pancreatic duct was involved. The area radiologically suspected to be the mass lesion showed features of pancreatitis without discrete mass. In addition, several ducts showed neutrophilic duct injury similar to granulocytic epithelial lesions observed in type 2 AIP. Immunohistochemistry revealed the aberrant expression of IL‐8 in the pancreatic ductules and infiltrating CD3‐positive T‐lymphocytes, findings recently identified in type 2 AIP. The present case is not typical for either type 2 AIP or other known conditions, but extreme examples of type 2 AIP may present with ductal obstruction because of severe neutrophilic duct injury. IL‐8 immunostaining may also assist in establishing a diagnosis of type 2 AIP with an atypical presentation.     

Diets rich in saturated fat and fructose induce anxiety and depression‐like behaviours in the rat: is there a role for lipid peroxidation?

Epidemiological studies reveal associations between obesity/metabolic syndrome and mood disorders. We assessed behavioural changes in rats fed diets enriched in fat and fructose in different proportions and correlated the observed alterations with biochemical changes induced by the diets. Three groups of rats were used as follows: control (C) animals fed regular rat chow, rats fed high‐fat diet (HF) and rats fed high‐fat and high‐fructose diet (HFHF). HF and HFHF animals were also given a 10% fructose solution as drinking water. Behavioural and biochemical parameters were determined. Anxiety was measured by the open‐field and the social interaction test. Depression‐like behaviour was evaluated by the forced swimming test. The object recognition test was utilized to assess effects on memory. Diet‐exposed animals displayed signs of anxiety in the open‐field (HF rats had reduced central time; HFHF rats had reduced number of central entries) and in the social interaction test (decreased time of interaction in HF group). In the forced swimming test, the immobility time was prolonged in the HFHF group. While different measures of anxiety scores correlated with visceral adiposity and dyslipidemia, results from both social interaction and forced swimming tests were significantly associated with lipid peroxidation, which in turn also correlated with the metabolic parameters. The experimental diets did not affect the object recognition memory. Both experimental diets induced metabolic derangements in rats and provoked similar anxiety‐ and depression‐like behaviours. Lipid peroxidation seems to play a role in translating diet‐induced metabolic alterations into behavioural disorders.     

Is ADHD a valid disorder in children with intellectual delays?

To assess the validity of ADHD in children with mental retardation, we applied Robins and Guze's [Robins, E., and Guze, S.B. (1970). Establishment of diagnostic validity in psychiatric illness: Its application to schizophrenia. American Journal of Psychiatry, 126, 983-987.] criteria for determining the validity of a psychiatric disorder. We review the literature describing clinical correlates, family history, treatment response, laboratory studies, course, and outcome of children with ADHD and mental retardation. Although clearly an area in need of further research, there is preliminary evidence to suggest that ADHD is a valid psychiatric condition in children with mental retardation. Nevertheless, without knowing the base rates of ADHD symptoms in the mental retardation population, the positive predictive power and negative predictive power of ADHD symptoms in this population remain an open question. In addition to assessment of base rate symptoms, future research should consider what diagnostic algorithm may best be applied to the diagnosis of ADHD in mental retardation.     

Neonatal hyperphenylalaninemia, perinatal hemochromatosis, and renal tubulopathy: a unique patient or a novel metabolic disorder?

A neonate presented with hyperphenylalaninemia (HPA), with a persistently elevated phenylalanine/tyrosine ratio. The HPA was responsive to tetrahydrobiopterin (BH4). His clinical course was dominated by liver failure, associated with perinatal hemochromatosis. He also developed renal tubulopathy. HPA has not previously been reported in association with any of these features. We investigated the etiology of his condition, and discuss the possibility that this represents a novel single-gene disorder.