Epilepsia partialis continua in type 1 diabetes: evolution into epileptic encephalopathy with continuous spike-waves during slow sleep.

Hyperglycemic status may be rarely complicated by Epilepsia partialis continua (EPC) that usually responds to metabolic normalization. Anti-glutamic acid decarboxylase antibodies (GAD-Ab) play a pivotal role in the autoimmune process that leads to clinical onset of type 1 diabetes mellitus (T1DM). GAD-Ab have been recently reported in association with rare forms of refractory epilepsy, with or without association to T1DM. Here we describe a young patient who developed EPC five months after T1DM onset; GAD-Ab were detected in his cerebrospinal fluid with evidence of oligoclonal bands. His epileptic disorder evolved over time into drug-resistant epilepsy with continuous spike-waves during slow sleep and severe behavioral impairment. The role of both metabolic imbalance and GAD autoimmunity is discussed.

Hippocampal volume and cognitive performance in long-standing Type 1 diabetic patients without macrovascular complications.

AIMS: Hippocampal atrophy and memory deficits have been reported in Type 2 diabetes. Whether similar alterations occur in Type 1 diabetes is currently unknown. METHODS: In a case-control design, 13 Type 1 diabetic patients with at least 10 years' duration of disease, but free from clinical signs of macrovascular disease, were compared with age- and gender-matched control subjects. Hippocampal volume and measures of global cerebral cerebrospinal fluid (CSF) were determined from magnetic resonance imaging (MRI) scans. Cognitive functions were assessed using four neuropsychological tests. Mood and depression were measured by questionnaires. RESULTS: Hippocampal volume and memory did not differ between Type 1 diabetic patients and control subjects. However, a significantly increased amount of cerebral CSF suggestive of mild cerebral atrophy was observed in the patients. In addition, deficits in psychomotor speed and selective attention were apparent. Eleven of 13 patients had retinopathy and/or nephropathy. Findings were unrelated to cerebrovascular disease, white matter disease or silent strokes. CONCLUSIONS: Results from our small study in Type 1 diabetic patients do not support findings from previous studies of Type 2 diabetic patients demonstrating reductions in hippocampal volume and impaired memory. On the contrary, we observed evidence for mild cerebral atrophy and impaired psychomotor speed and selective attention. This is in line with some previous studies in Type 1 diabetes. If replicated in larger studies, our findings would support the idea that the effects on brain function and structure differ between Type 1 and Type 2 diabetes.

The role of the biochemistry department in the diagnosis of pituitary apoplexy.

A 47-year-old man presented with severe clinical hypoglycaemia. He had long-standing insulin-dependent diabetes with previously good glycaemic control. Intense headaches and vomiting initiated hospitalization. A brain computed tomography (CT) scan was normal, and a lumbar puncture showed elevated cerebrospinal fluid (CSF) protein [0.67 g/L; normal range (NR) 0.15-0.45 g/L], suggesting resolving viral meningitis. Routine thyroid function tests were abnormal (free thyroxine 10.6 pmol/L, NR 9-22.5 pmol/L; thyroid-stimulating hormone 0.16 mU/L, NR 0.35-5 mU/L). In the absence of evident thyroid therapy, the laboratory policy required an urgent cortisol assay to be added; this was very abnormal (42 nmol/L), suggesting hypopituitarism. Later analysis showed that concentrations of gonadotrophins and adrenocorticotrophin were low. An urgent pituitary magnetic resonance imaging scan revealed an unsuspected pituitary tumour with recent haemorrhage (pituitary apoplexy). The patient was given intravenous hydrocortisone and then stabilized on oral hydrocortisone, thyroxine and mesterolone. He made a full recovery and the hypoglycaemia resolved. The normal brain CT scan was falsely reassuring and the CSF protein was not due to viral meningitis but to haemorrhage into the pituitary tumour. If laboratory policy had not required the urgent cortisol assay be added, the diagnosis of hypopituitarism would have been delayed or even missed altogether. This could have led to the death of the patient.

Tremor of the mouth floor and anti-glutamic acid decarboxylase autoantibodies.

Involuntary movements of the mouth can present as palatal tremor, which is frequently associated with hypertrophy of the inferior olivary nucleus and can be accompanied by contraction of other muscles of the head. We report the case of a 39-year-old man with autoimmune thyroiditis and diabetes who complained of involuntary rhythmic tremor involving the muscles of the floor of the mouth, which interfered with breathing and swallowing. Cerebrospinal fluid (CSF) examination showed the presence of oligoclonal bands and screening for anti-neuronal antibodies revealed high titres of anti-glutamic acid decarboxylase autoantibodies (GAD-Ab). Tremor responded to treatment with benzodiazepines. The correlation between the tremor and antibody positivity is unclear although an alteration of the gabaergic system mediated by the antibodies may be hypothesised on the basis of an inflammatory CSF profile.

Stiff person syndrome: quantification, specificity, and intrathecal synthesis of GAD65 antibodies.

OBJECTIVE: To characterize the specificity of anti-GAD(65) antibodies in patients with stiff person syndrome (SPS), quantify antibody titers, and examine antibody production within the CNS. METHODS: The authors studied 18 patients with SPS and positive serum immunoreactivity to gamma-aminobutyric acid (GABA)-ergic neurons. The reactivity of serum and CSF to purified GAD antigen was examined by Western blots, and the anti-GAD(65) antibody titers in serum and CSF were quantified by ELISA and compared with 70 disease controls (49 with other autoimmune disorders and 11 with insulin-dependent diabetes mellitus). The intrathecal synthesis of anti-GAD(65) IgG was calculated, and the functional significance of the antibodies was examined by measuring the GABA levels in the CSF. RESULTS: The serum and CSF of all selected patients with SPS had high anti-GAD(65) titers (from 7.0 to 215 microg/mL in serum and from 92 to 2500 ng/mL in CSF) and immunoreacted strongly with recombinant GAD(65) on Western blots and with GABA-ergic neurons on rat cerebellum. Among controls, only the serum of eight patients with insulin-dependent diabetes mellitus had low anti-GAD(65) antibody titers (from 200 to 1760 ng/mL) but no reactivity to recombinant GAD(65). The CSF showed oligoclonal IgG bands in 10 (67%) of 15 patients and an increased anti-GAD(65)-specific IgG index in 11 (85%) of 13. The mean level of GABA in the CSF was lower in patients with SPS than in controls. CONCLUSIONS: In patients with SPS, there is marked intrathecal antibody response against neuronal GAD(65) epitopes, indicating a clonal B cell activation in the CNS. Anti-GAD(65) antibodies at high titers, when confirmed with immunoblots, are highly specific for SPS and appear to impair GABA synthesis.

Catecholamine concentrations in venous plasma and cerebrospinal fluid in normal and complicated pregnancy.

The concentrations of adrenaline and noradrenaline were determined in venous plasma and cerebrospinal fluid (CSF) of 41 pregnant women at term scheduled for elective or 'hot' caesarean section and in 7 healthy non-pregnant women scheduled for elective surgery. Group 1: 10 pregnant women at term with a normal history of their pregnancy; group 2: like group 1, but in active labour for more than 4 h; group 3: 10 pregnant women with insulin-dependent diabetes mellitus with or without slightly elevated arterial blood pressure; group 4: 11 women with pre-eclampsia gravis; group 5: 7 healthy non-pregnant women of fertile age. The highest values of mean arterial blood pressure and of venous plasma noradrenaline were found in the pre-eclamptic group 4, mean arterial blood pressure and plasma noradrenaline levels correlated to each other. However, concentrations of noradrenaline in CSF in group 4 did not differ significantly from the other groups. It is speculated that a different origin of hypertension may be the reason for the normal noradrenaline concentrations in CSF. This finding is in contrast to earlier findings in which noradrenaline levels in CSF were elevated in patients with essential hypertension.