Alterations in Polysomnographic (PSG) profile in drug-na?ve Parkinson's disease

Objective:

We studied the changes in Polysomnographic (PSG) profile in drug-naïve patients of Parkinson''s disease (PD) who underwent evaluation with sleep overnight PSG.

Materials and Methods:

This prospective study included 30 with newly diagnosed levodopa-naïve patients with PD, fulfilling the UK-PD society brain bank clinical diagnostic criteria (M:F = 25:5; age: 57.2 ± 10.7 years). The disease severity scales and sleep related questionnaires were administered, and then patients were subjected to overnight PSG.

Results:

The mean duration of illness was 9.7 ± 9.5 months. The mean Hoehn and Yahr stage was 1.8 ± 0.4. The mean Unified Parkinson''s Disease Rating Scale (UPDRS) motor score improved from 27.7 ± 9.2 to 17.5 ± 8.9 with sustained usage of levodopa. Nocturnal sleep as assessed by Pittsburgh Sleep Quality Index (PSQI) was impaired in 10 (33.3%) patients (mean PSQI score: 5.1 ± 3.1). Excessive day time somnolence was recorded in three patients with Epworth Sleepiness Scale (ESS) score ≥ 10 (mean ESS score: 4.0 ± 3.4). PSG analysis revealed that poor sleep efficiency of <85% was present in 86.7% of patients (mean: 68.3 ± 21.3%). The latencies to sleep onset (mean: 49.8 ± 67.0 minutes) and stage 2 sleep (36.5 ± 13.1%) were prolonged while slow wave sleep was shortened. Respiration during sleep was significantly impaired in which 43.3% had impaired apnoea hyperpnoea index (AHI) ≥5, mean AHI: 8.3 ± 12.1). Apnoeic episodes were predominantly obstructive (obstructive sleep apnea, OSA index = 2.2 ± 5.1). These patients had periodic leg movement (PLM) disorder (56.7% had PLM index of 5 or more, mean PLMI: 27.53 ± 4 9.05) that resulted in excessive daytime somnolence.

Conclusions:

To conclude, sleep macro-architecture is altered in frequently and variably in levodopa-naïve patients of PD and the alterations are possibly due to disease process per se.     

Incidence (1988-97) and prevalence (1997) of multiple sclerosis in Västerbotten County in northern Sweden

Objective: To investigate the incidence and prevalence of multiple sclerosis in Västerbotten County in northern Sweden. Methods: Multiple sources were used in the case identification process. Follow up interviews with clinical examinations were undertaken and, when indicated, additional paraclinical investigations were done. In this way case ascertainment was assured and supplemental clinical data were collected. The incidence rate was based on symptom onset. Onset adjusted prevalence was applied. Results: The crude incidence rate of multiple sclerosis in 1988–97 in Västerbotten County was 5.2/10⁵ (95% confidence interval, 4.4 to 6.2): 6.7/10⁵ (6.0 to 8.3) in women and 3.7/10⁵ (2.7 to 4.9) in men. The onset adjusted prevalence for 31 December 1997 was 154/10⁵ (139 to 170): 202/10⁵ (179 to 228) in women and 105/10⁵ (89 to 125) in men. When compared with a previous estimate of prevalence, a yearly 2.6% increase in prevalence between 1990 and 1997 was found, mainly attributable to a higher incidence than mortality. Conclusions: The present incidence rate and prevalence confirms earlier findings that Västerbotten is a high risk area for multiple sclerosis. The adjusted incidence was twice as high as the incidence from 1974–88 in the only previous Swedish population based study from Göteborg, but comparable with other recent Fennoscandian multiple sclerosis incidence rates.     

Serum brain-derived neurotrophic factor (BDNF) levels in attention deficit–hyperactivity disorder (ADHD)

It has been proposed that the neurotrophin brain-derived neurotrophic factor (BDNF) may be involved in attention deficit–hyperactivity disorder (ADHD) etiopathogenesis. Alterations in BDNF serum levels have been observed in childhood/adulthood neurodevelopmental pathologies, but no evidence is available for BDNF serum concentrations in ADHD. The study includes 45 drug-naïve ADHD children and 45 age–sex matched healthy subjects. Concentration of serum BDNF was determined by the ELISA method. BDNF serum levels in patients with ADHD were not different from those of controls (mean ± SD; ADHD: 39.33 ± 10.41 ng/ml; controls: 38.82 ± 8.29 ng/ml, t = ?0.26, p = 0.80). Our findings indicate no alteration of serum BDNF levels in untreated patients with ADHD. A further stratification for cognitive, neuropsychological and psychopathological assessment in a larger sample could be useful to clarify the role of BDNF in the endophenotype characterization of ADHD.     

Die Mismatch-Negativität (MMN) in der Schizophrenieforschung

Mismatch negativity (MMN) represents an event-related component of the auditory evoked potentials at about 100-250 ms, evoked by discernible changes in an ongoing uniform acoustic stimulation. The current paper reviews all recently published MMN studies in the field of schizophrenia research. A reduced MMN in schizophrenic patients is found in the majority of the studies. This deficit is likely to be related to the disorder, since antipsychotic medication seems to have little influence on these results. Interestingly, a reduced MMN is also found in first-degree relatives of patients. Clear evidence for a hemispheric lateralization of the MMN reduction in schizophrenic patients is lacking. A hypofunction of the N-methyl-D-aspartate (NMDA) receptor is discussed as a possible explanation of this deficit.     

Variations in the monoamine oxidase-inhibitory activity (“tribulin?”) in pig's urine

Summary Sandler and his colleagues (see Sandler, 1982) have demonstrated the presence of an endogenous inhibitor of the enzyme monoamine oxidase (MAO) and of benzodiazepine receptor binding in the urine and blood plasma of man and rat. The concentrations of this material increased under stress conditions and it has been named tribulin. In the present experiments MAO-inhibitory activity was found in extracts of urine and plasma samples of domestic pigs. Evidence was obtained that the inhibitory activity was higher when pigs experienced slight discomfort. Thus it appears that pigs produce a substance similar to tribulin. It may become possible to use such MAO-inhibitory activity as an indicator in the assessment of interaction with the environment in pig husbandry.     

Oligodendrocytes within astrocytes (“emperipolesis”) in the white matter in Creutzfeldt-Jakob disease

The occurrence of oligodendrocytes within astrocytes (emperipolesis) has been described in demyelinating lesions in cases of multiple sclerosis and also in other non-demyelinating disorders. We found that this finding was common in the cerebral white matter of patients with Creutzfeldt-Jakob disease (CJD). Eight consecutive autopsy cases of sporadic CJD were reviewed, and in every case the gray matter exhibited classical histopathological features of CJD. In five cases with a long clinical course, the cerebral white matter was severely involved, and both axons and myelin sheaths were lost markedly. Within this devastated white matter, many hypertrophic astrocytes were found to engulf one to several oligodendrocytes within their cytoplasm (emperipolesis). The oligodendroglial nature of the engulfed cells was corroborated by nuclear immunoreactivity for anti-human Olig 2 antibody. In the remaining three cases, whose clinical course was short, the cerebral white matter was relatively well preserved, and emperipolesis was not or only very rarely found. The prevalence of emperipolesis of this type in the white matter in CJD was well correlated with the severity of the white matter lesions.     

Is silica involved in neuritic (senile) plaque formation?

Summary The agent responsible for inducing neuritic (senile) plaque formation in senile dementia of the Alzheimer's type and in the ageing non-demented brain is unknown. Other workers have detected a high concentration of silicon in the rims and cores of senile neuritic plaques. We have therefore looked at whether the reaction of brain tissue to silica particles resembles a neuritic plaque. In this study both fine (10 nm) and coarse (<5 m) particles of silica have been introduced into the brains of rats and mice using a wide range of doses and several methods of administration. The reaction of the brain to the presence of the silica was examined by light and electronmicroscopy up to one year after the injection.The presence of silica particles in the brain resulted in the proliferation of fibrous astrocytes and macrophages and strongly stimulated the production of collagen fibres. Degeneration of some adjacent axons and axon terminals occurred, but there was no detectable deposition of amyloid which is characteristic of senile plaques. Coarse particles of silica invariably produced a more intense reaction than fine particles. The reaction of the brain did not diminish with time within one year of injection.The possible significance of the presence of silica in the plaque as a secondary phenomenon is discussed.Supported by a National Health and Medical Research Council Grant     

Über das Rauwolfia-Alkaloid Reserpin (Serpasil) in der Psychiatrie

Zusammenfassung Es wird über die Fortsetzung der klinischen Prüfung des Rauwolfia, Alkaloides Reserpin (Serpasil) berichtet. Die neuen Untersuchungen unserer Klinik erstreckten sich über 8 Monate und umfaßten 179 abgeschlossene Kuren mit Serpasil.Es wurden behandelt: Akute und chronische Schizophrenien mit verschiedenen Hauptsymptomen, leukotomierte Schizophrene mit Rezidiven, manische und depressive Verstimmungen verschiedener Ätiologie, Ausnahmezustände bei Psychopathen, Alkoholikern und anderen psychiatrisch Kranken.Als wesentlichstes Phänomen psychiatrischer Wirksamkeit zeigte sich die Sedation, besonders in der schlafreichen Initialphase. Die selektive Stammhirnwirkung wird diskutiert.Vorläufige Indikationen sind: Erregungszustände jeder Genese, Spannungen, innere Unruhe, Stupor, Negativismus, Verstimmungen und Zwangsimpulse. Kontraindiziert ist Serpasil bei Ulcus ventriculi et duodeni und Thrombosen. Sorgfältige Beachtung körperlicher Komplikationen ist notwendig.Als zweckmäßige Dosierung ergab sich 2×2,5 mg—2×5 mg i.m. bis zur anhaltenden Besserung der Hauptsymptome, dann Übergang auf Tabletten-Medikation mit langsamem Reduzieren der Dosis (von 2×5 bis 2×1 mg Tabletten pro die).Die somatischen Begleiterscheinungen werden ausführlich dargestellt. Im Vordergrund stehen Kreislaufsymptome, die keine unüberwindliche Schwierigkeit bedeuten und einzelne extrapyramidale und vegetative Symptome bis zur Ausbildung eines (reversiblen) Parkinson-Syndroms.Herrn Prof. Dr. Gustav Bally, Zürich, in Verehrung zugeeignet.     

Pioneers in neurology: Felix Plaut (1877–1940)

Journal of Neurology -     

Is protein kinase C (PKC) involved in nociception?

The study was designed to determine whether the protein kinase C (PKC) is involved in nociceptive c-Fos expression and the concomitant signaling processes of endogenous opioid-like substances (OLS) that modulate c-Fos expression in the spinal dorsal horn following formalin injection into the unilateral hindpaw in rats by using immunocytochemical techniques. In the first part of experiments in which rats were pretreated with intrathecal (i.t.) chelerythrine (Chel), an inhibitor of PKC, the nociceptive c-Fos-like immunoreactive (Fos-LI) neurons in the lumbar dorsal horn ipsilateral to the formalin injection were significantly suppressed with a reduction rate of 60.3% (p < .001) as compared to that in the control group with i.t. saline. In the second part of experiments in which rats were pretreated with i.t. naloxone (Nal), the nociceptive Fos-LI neurons were significantly increased by 53.2% (p < .01) as compared to that in the control group; however, when rats were pretreated with combined i.t. Nal + Chel, the nociceptive Fos-LI neurons exhibited a percentage reduction similar to that in group with i.t. Chel alone, although the real number of Fos-LI neurons in group with i.t. Nal + Chel still significantly surpassed that in group with i.t. Chen only. These results suggest that: (1) PKC may play an important role in the induction of nociceptive c-Fos expression; (2) nociceptive c-Fos expression is subject to the modulation of endogenous OLS that suppress the nociceptive responses of the dorsal horn neurons; and (3) PKC may not be involved in the signaling processes by which the endogenous OLS modulate the nociceptive c-Fos expression in the spinal level.     

Antibodies to Domain I of β(2)Glycoprotein I are in close relation to patients risk categories in Antiphospholipid Syndrome (APS)

Introduction

Antiphospholipid Syndrome (APS) is characterized by the presence of circulating antiphospholipid antibodies in patients with thrombosis or pregnancy morbidity. Antibodies involved in these disorders are mainly those directed against β₂-Glycoprotein I (β₂GPI) with the major epitope apparently located on discontinuous antigen with several parts of Domain I (DmI) involved. The relation between anti-DmI antibodies and patients’ risk categories is unknown.

Materials and Methods

The synthetic full-length and correctly-folded DmI (1–64) to set up a competitive inhibition enzyme-linked immunoadsorbent assays (ELISA) was used. Plasma of 22 patients with APS and triple positivity [Lupus Anticoagulant positive (LAC+), IgG anti-cardiolipin positive (aCL+), IgG anti-β₂GPI positive (a β₂GPI +)], 15 with double positivity (IgG aCL+, IgG aβ₂GPI+), 9 with single positivity (IgG aβ₂GPI+) and 20 controls were evaluated.

Results

Median of percentage inhibition was 25.5% [interquartile range (IQR)17.2-33.0] in triple positive patients. Significantly lower inhibition was observed in patients with double positivity, median inhibition 5.0% (IQR 0.0-27.0) and in patients with single positivity median inhibition was 2.0% (IQR 0.5-8.0) (p < 0.0001). No inhibition was detected in control subjects or using β₂GPI peptides (40–52 and 57–70), or when antithrombin, an insignificant control protein was used.

Conclusions

High risk patients with APS and triple laboratory positivity as compared with double and single positivity patients have significantly higher titre of anti-DmI antibodies as evaluated by an inhibition test.     

Selective naming (and comprehension) deficits in Alzheimer's disease?

The study addresses the issue of the selective preservation of verbs in Alzheimer's disease (AD). Twenty three AD patients and age-matched controls named pictures of objects and actions and took part in a word-picture verification task. The results for picture naming revealed that both patients and controls were faster and produced more target responses for objects than actions. In the comprehension task, accuracy levels were comparable for nouns and verbs, but response times were longer for verbs. Although patients were more error prone and had longer latencies in both tasks than controls, the only qualitative difference in performance between the groups was in response to trials with semantically related foils in the word-picture verification task. Patients were particularly error prone in this condition. We conclude that the results do not provide support for the notion that verbs are selectively preserved in AD. They also do not provide conclusive evidence for claims that depressed naming and comprehension is (always) due to loss of semantic knowledge or inadequate access to semantic knowledge. Finally, we discuss the findings in relation to comparable investigations in patients with semantic dementia.     

Changes in severity of psychosocial difficulties in adolescents accessing specialist mental healthcare in England (2009–2014)

In England, clinicians and professional organisations report that higher numbers of adolescents with more severe psychosocial difficulties are accessing specialist services. A lack of national data on patterns of access to specialist services means there is limited information to inform policy. We examined whether severity of psychosocial difficulties in adolescents accessing mental healthcare has changed over time. Adolescents seen in specialist child mental healthcare in 2009 vs. 2014 were matched on demographics and problem types using propensity score matching; final sample N = 2776 adolescents. We found: 1) stability over time in overall severity of difficulties, 2) an increase in severity of young women's emotional problems, and 3) a decrease in adolescents' conduct problems. The findings suggest the intriguing possibility that the criteria for accessing mental healthcare are not universally rising, but rather the patterns in access to specialist services may mirror epidemiological changes in severity of psychosocial difficulties in the population.     

Pioneers in neurology: Abraham Myerson (1881–1948)

Journal of Neurology -     

How is kyotorphin (Tyr-Arg) generated in the brain?

Kyotorphin (Tyr-Arg) was rapidly degraded in the brain homogenates and purified membrane-bound aminopeptidase from monkey brains. The degradation of kyotorphin by these preparations was effectively inhibited by bestatin. When brain homogenates or slices were incubated with bestatin, kyotorphin was accumulated time-dependently in a rate of 1.0 or 2.1 pmol/mg protein/hr, respectively. The bestatin-induced kyotorphin accumulation was inhibited by leupeptin, p-chloromercuribenzoate, but not phenylmethylsulfonylfluoride or diisopropylphosphate. The kyotorphin accumulation was concentrated in the P2 (crude mitochondrial) fraction, particularly in the particulate or synaptosomal fraction. These findings suggest that kyotorphin may be generated in vitro from precursor proteins by membrane-bound, leupeptin-sensitive "kyotorphin converting enzymes" in close vicinity to membrane-bound aminopeptidase which rapidly degrades kyotorphin generated.     

Psychopathology in adolescent and young adult criminal offenders (15–21 years) in Sweden

Background This study examined rates of psychopathology among adolescent and young adult serious offenders referred to pre-sentence forensic psychiatric services and compared patterns of psychiatric morbidity with adult forensic referrals and age-matched general psychiatric inpatients. Methods In Sweden, criminal offenders can be referred for an extensive court-ordered pre-sentence inpatient forensic psychiatric examination (FPE). Data on all 3,058 of these offenders (90% male, mean age = 35.3 years) during 1997–2001 were obtained from the National Board of Forensic Medicine. We compared DSM-IV psychiatric diagnoses across age bands 15–17 years (N = 60), 18–21 years (N = 300) and 22 years and older (N = 2,698). Comparative data by age bands were also obtained for inpatient diagnoses among individuals admitted to general psychiatric hospitals. Results Compared with the adult forensic psychiatric examinees, those aged 15–17 years and 18–21 years had higher rates of depression, and childhood and developmental disorders but lower rates of psychosis, bipolar disorder, and substance use disorders. Compared with general psychiatric inpatients, offenders aged 15–17 years had higher prevalences of depression and attention-deficit or disruptive disorders and lower ones of alcohol and drug misuse disorders. Conclusions There are significant differences in patterns of psychiatric morbidity in adolescent and young adult offenders that come into contact with psychiatric services compared with older offenders and adolescent psychiatric inpatients. This suggests that the development of health services addressing the psychiatric needs of younger offenders needs to draw on information on their specific mental health needs.     

Decrease in brain soluble amyloid precursor protein β (sAPPβ) in Alzheimer's disease cortex

Amyloid-β peptide (Aβ) is generated by sequential cleavage of the amyloid precursor protein (APP) by β-site amyloid precursor protein cleaving enzyme 1 (β-secretase, or BACE1) and γ-secretase. Several reports demonstrate increased BACE1 enzymatic activity in brain and cerebrospinal fluid (CSF) from Alzheimer's disease (AD) subjects, suggesting that an increase in BACE1-mediated cleavage of APP drives amyloid pathophysiology in AD. BACE1 cleavage of APP leads to the generation of a secreted N-terminal fragment of APP (sAPPβ). To relate BACE1 activity better to endogenous APP processing in AD and control brains, we have directly measured brain sAPPβ levels using a novel APP β-site specific enzyme-linked immunosorbent assay. We demonstrate a significant reduction in brain cortical sAPPβ levels in AD compared with control subjects. In the same brain samples, BACE1 activity was unchanged, full-length APP and sAPPα levels were significantly reduced, and Aβ peptides were significantly elevated. In conclusion, a reduction in cortical brain sAPPβ together with unchanged BACE1 activity suggests that this is due to reduced full-length APP substrate in late-stage AD subjects. These results highlight the need for multiparameter analysis of the amyloidogenic process to understand better AD pathophysiology in early vs. late-stage AD.