Olfactory dysfunction in patients with narcolepsy with cataplexy is restored by intranasal Orexin A (Hypocretin-1).

Until recently, olfactory dysfunction was an unknown feature of narcolepsy. Orexin A, also called hypocretin-1, is abnormally decreased or undetectable in the cerebrospinal fluid of narcoleptic patients with cataplexies. As hypothalamic orexin-containing neurons project throughout the entire olfactory pathway, from the olfactory mucosa to the olfactory cortex, disturbed orexinergic transmission may crucially be involved in impaired olfactory performance of narcolepsy patients. In our study we analysed the olfactory performance (threshold, discrimination, identification and sum score of these measurements, the TDI score) of narcoleptic patients with cataplexies (n = 10) and of age-, gender-, BMI- and smoker/non-smoker-matched healthy controls (n = 10). We then in a double-blind, randomized, placebo-controlled cross-over design applied orexin A intranasally to seven of the patients and measured 2-phenyl-ethyl alcohol (PEA) single-staircase odour detection thresholds. Compared to the controls, patients showed significantly lower scores for olfactory threshold (patients: median 8.0, range 4.0-10.5; controls: median 9.4, range 7.5-13.3; P < 0.05), discrimination (patients: median 12.5, range 10-15; controls: median 15.0, range 12-16; P < 0.005), identification (patients: median 13.0, range 10-16; controls: median 14.0, range 13-16; P < 0.05) and TDI score (patients: median 33.4, range 30-36; controls: median 38.4, range 35-43; P < 0.0001). In all patients, the PEA olfactory threshold score increased after administration of orexin A (median 11.5, range 6.5-13.25) compared to placebo (median 7.75, range 6.25-11.25; P < 0.05). Our results support the hypothesis that mild olfactory dysfunction is an intrinsic symptom of narcolepsy with cataplexies. The observation that intranasal orexin A restores olfactory function is in favour of this hypothesis. Furthermore, our data support that the pathophysiological mechanism underlying olfactory dysfunction in narcolepsy is the lack of CNS orexin.

Neuropsychological findings in patients with intraventricular tumors.

BACKGROUND: Intraventricular tumors are quite rare and become symptomatic with hydrocephalus-related signs such as headache, double vision, and seizures. Also, most of the patients show neuropsychological deficits, especially memory problems and lack of attention. METHODS: We reviewed the charts and computed tomographic/magnetic resonance images of 15 patients with tumors of the lateral and third ventricle, who were also examined by a neuropsychologist pre- and postoperatively. Neuropsychological testing included tests of attention, memory, executive functions, and concentration. RESULTS: Between 1995 and 2003, 7 patients with colloid cysts of the third ventricle (3 men, 4 women; mean age, 38 years), 5 patients with meningiomas of the lateral ventricle (2 men, 3 women; mean age, 51 years), and 3 patients with astrocytomas and ependymoma (2 men, 1 woman; mean age, 38 years) were treated. All patients with colloid cysts and meningiomas showed mental changes, especially attention and memory deficits. Symptoms improved markedly after surgical intervention. The 3 patients with astrocytoma and ependymoma showed normal results pre- and postoperatively. CONCLUSION: Neuropsychological testing is very useful in patients with intraventricular lesions and important for follow-up examinations. It should be included in every workup examination in this small patient group.

Clinical experiences with oligoastrocytomas WHO grade II and III.

Between April 1991 and June 2002, 39 patients with an histologically proven oligoastrocytoma WHO grade II and III were operated on in our department. Twenty-two patients were male and 17 female. Mean age was 42 years (20-67 years). The tumor was localized in the frontal lobe in 22 patients, in the temporal lobe in seven patients, in the parietal lobe in nine patients and in the occipital lobe in one patient. The leading clinical symptoms were seizures in 33 patients. Seventeen patients were operated on under local anesthesia. One operation was performed in 22 patients, two operations in eight, three operations in five, four operations in three and six operations in one patient. Histological examination showed oligoastrocytoma WHO grade II in 12 patients and WHO grade III in 27 patients. Postoperative radiotherapy was performed in 33 patients and chemotherapy in six patients. One female patient developed spinal drop metastases 10 months after the operation. One patient with a primary oligoastrocytoma grade II and five patients with a primary oligoastrocytoma grade III died during follow-up. The follow-up period was between 6 months and 25 years (mean 7 years 6 months).

Does the cerebellum contribute to specific aspects of attention?

We present data on attentional and neuropsychological functions of 16 patients with focal cerebellar lesions (13 tumours, 3 haematomas) compared to normative test data, and to 11 control subjects matched for age, gender, and years of education. Patients showed distinct deficits in qualitative aspects of a divided attention task, and in a working memory task. Performance in selective attention was unimpaired. The results support the concept that the cerebellum plays a role not only in motor, but also in higher cognitive functions. They are discussed on the basis of the idea that prediction and preparation are fundamental functions of the cerebellum. Therefore, the results confirm the idea that cerebellar lesions lead to reduced performance in specific attention tasks.

Psychological, allergic, and toxicological aspects of patients with amalgam-related complaints.

BACKGROUND: To deepen the understanding of the numerous unspecific complaints which are related to the dental material amalgam both in patients and physicians, an interdisciplinary case-control study regarding toxicological, allergic, psychological and psychiatric aspects was conducted. Forty patients with amalgam-associated complaints were compared to a well-matched group of 40 amalgam bearers without complaints. METHODS: Patients and controls underwent a dental examination, which included recording of the quantity, surface area and quality of amalgam fillings, a determination of the mercury load in blood and urine, an allergy examination including patch testing with amalgam and a psychometric assessment with questionnaires noting coping strategies (ABI-UMW-P), interpersonal problems (Inventory of Interpersonal Problems) and self-consciousness (SAM), the NEO Five-Factor Inventory, Symptom Checklist-90-R, Beck Depression Inventory and a screening instrument for somatoform disorders. RESULTS: Patients and controls did not differ with respect to mercury concentrations in body fluids. Only 1 patient was found to have a positive amalgam patch test; various other allergies could be determined in 28% of patients (n = 11). Patients had higher levels of psychic distress, a higher incidence of depression and somatization disorders as well as different styles of coping with anxiety compared to controls. CONCLUSIONS: No indication for mercury intoxication or amalgam allergy as a cause of the patients' complaints could be found. The theory of amalgam-related complaints as an expression of underlying psychic problems is supported. Treatment should focus on somatization and changing coping and attribution styles.