Subclinical sensory abnormalities in unaffected PINK1 heterozygotes

Background   Mutations in the PINK1 gene, encoding a mitochondrial protein kinase, represent the second cause of autosomal recessive parkinsonism (ARP) after Parkin. While homozygous or compound heterozygous mutations in these genes are unequivocally causative of ARP, the role of single heterozygous mutations is still largely debated. An intriguing hypothesis suggests that these mutations could represent a risk factor to develop parkinsonism, by contributing to nigral cell degeneration. Since the substantia nigra plays an important role in temporal processing of sensory stimuli, as revealed from studies in idiopathic PD, we sought to investigate whether any subclinical sensory abnormalities could be detected in patients with PINK1- related parkinsonism and in unaffected PINK1 heterozygous carriers. Methods   We adopted a psychophysical method, the temporal discrimination paradigm, to assess PINK1 homozygous patients, unaffected relatives who were heterozygous carriers of the same mutations and healthy control subjects. Temporal discrimination threshold (TDT) and temporal order judgement (TOJ) for pairs of tactile, visual or visuo-tactile stimuli were measured according to a standardized protocol. Findings   Higher mean tactile and visuo-tactile TDTs and TOJs were detected in PINK1 mutation carriers, including not only homozygous patients but also healthy heterozygotes, compared to control subjects (for all comparisons, p < 0.001). Interpretation   In clinically unaffected subjects, the mere presence of a heterozygous PINK1 mutation is sufficient to determine sensory alterations which can be disclosed by a psychophysical task. Deficits in temporal processing might be considered as subclinical signs of alteration at least in PINK1-related parkinsonism.     

Subclinical lithium neurotoxicity: correlation of neural conduction abnormalities and serum lithium level in manic-depressive patients with lithium treatment

Nerve conduction velocities (NCVs) and multimodality evoked potentials were studies in 28 manic-depressive patients under lithium prophylaxis with serum lithium levels between 0.320 and 0.980 mEq/L. Slowing of motor and sensory NCVs and prolonged central neural conduction times obtained from somatosensory and brainstem auditory evoked potentials were found to correlate with serum lithium levels. Lithium-induced changes in cell membrane conductivity and in the synaptic transmission are considered responsible for the neurotoxic effects of lithium.     

Electrodiagnostic abnormalities in 15 patients with posttraumatic syringomyelia: pre- and postoperative studies

A review of 15 patients with posttraumatic syringomyelia indicates that the most reliable electrodiagnostic criteria for the diagnosis of syrinx are the loss of motor unit numbers with increase in motor unit amplitude and duration nd synchronous firing. Prolongation of F wave latency in a previously stable patient is a useful observation. Return of function and improvement of F wave latencies can occur rapidly following decompression of the syrinx. Forty per cent of the patients studied had concomitant involvement of at least one peripheral nerve as one would expect invoking the double crush hypothesis.     

Familial aspects of CT scan abnormalities in chronic schizophrenic patients

To investigate the possibility that lateral cerebral ventricular size may be under genetic control, we compared the computed tomography (CT) scans of 17 healthy siblings from 7 normal sibships. The CT scans of 10 chronic schizophrenic patients and 12 of their nonschizophrenic siblings were also compared. A trend was found for a correlation of ventricular size between siblings in the healthy sibships (ICC = 0.25, p = 0.1) but not in the schizophrenic sibships (ICC = -0.05). In each sibship the schizophrenic patient had the largest ventricles; in seven cases they exceeded the normal range. Although the discordant siblings were all well within the normal range, their ventricles were larger (p = 0.001) than those of the controls. The findings suggest a genetic component to ventricular size in healthy individuals and that CT findings in schizophrenics are not coincidental familial traits but markers of the illness. The implications of the findings in the discordant siblings are discussed.     

Oxidative stress and neopterin abnormalities in schizophrenia: A longitudinal study

Oxidative stress abnormalities have been proposed to explain the pathogenesis of schizophrenia. The present study examined neopterin and oxidative stress abnormalities in schizophrenia patients before and after treatment. Serum neopterin, total anti-oxidants, nitrites and thiols in antipsychotic-naïve schizophrenia patients (n = 45) were assessed at baseline before treatment in comparison with healthy controls (n = 43). The schizophrenia patients on treatment were followed up for 3 months and these parameters were reassessed (n = 32). In comparison to healthy controls, schizophrenia patients had significantly higher levels of neopterin and nitrites and significantly lower levels of anti-oxidants before treatment. During follow-up assessments in schizophrenia patients after treatment with antipsychotics, there was a significant decrease in the neopterin levels and significant increase in anti-oxidant levels. Our study observations support increased oxidative stress in schizophrenia that improves with antipsychotic treatment.     

Psychodynamic therapy in chronic pain patients: a systematic review

Psychoanalysis has made fundamental contributions to our understanding of somatoform pain disorder; however, psychodynamic therapy procedures have not been accorded their due recognition in the treatment of chronic pain. This is due to the inadequate differential indication for the employment of psychodynamic treatment methods, on the one hand, and to the refusal of most of the psychoanalysts to modify the standard psychoanalytic procedures in accordance with the requirements of pain treatment. This article reviews evidence of the modification of psychodynamic therapy procedures and their outcome in chronic pain patients in the context of past research. We conducted a systematic computer-based literature research employing MEDLINE, EVIDENCE BASED MEDICINE, and PSYNDEX data-bases between 1980 and 2000. Psychodynamic therapy procedures are indicated in the first instance for patients with psychic co-morbidity and those with somatoform pain disorder. A modification of the psychotherapeutic technique, involving an approach that is more structured and is also rather supportive at least at the beginning, is necessary. While employing psychodynamic methods in the treatment of pain patients, greater importance should be attached to the physical level and to the 'holding function' of the therapist than is usually the case with the conventional psychoanalytic therapy procedures.     

Subclinical hyperthyroidism seems not to have a significant impact on systemic anticoagulation in patients with coumarin therapy

There is little data regarding the impact of subclinical hyperthyroidism on coagulation metabolism in patients undergoing systemic anticoagulation therapy with coumarin derivates. In this retrospective analysis we studied 233 patients with benign thyroid disorders receiving therapeutic iodine-131, as well as concomitant systemic anticoagulation therapy (subclinical hyperthyroidism: n = 178; overt hyperthyroidism: n = 15; euthyroidism: n = 40). Multivariate regression analyses were performed in the total study population as well as in the subgroup of patients with subclinical hyperthyroidism to identify the possible impact of several variables on anticoagulation therapy, large enough to push the International Normalized Ratio (INR) level out of the therapeutic range (INR <2.0 or >3.0). Therapy with antibiotics or nitrates was significantly associated with INR-values >3.0 in the total population, while ACE inhibitors were associated with lower incidence of INR-values <2.0. In patients with subclinical hyperthyroidism, therapy with antibiotics was predictive of INR-values >3.0, whereas therapy with thyroid suppressive drugs or TSH-values <0.1 mU/l was associated with INR-values <2.0. Moreover, in a subgroup of 40 patients with the positive history of both subclinical hyperthyroidism and euthyroidism intraindividual comparison with regard to the possible impact on anticoagulation therapy was performed which failed to show any significant differences in INR-values between the two thyroid metabolic conditions. In conclusion, subclinical hyperthyroidism seems to have no significant impact on coagulation metabolism in patients receiving anticoagulation therapy.     

Structural abnormalities in the cerebral cortex of chronic schizophrenic patients.

Enlarged cerebral ventricles in chronic schizophrenic patients suggest a process of mild cerebral atrophy occurs in some. To see if this process involves the cerebral cortex, the widths of the Sylvian fissure, the interhemispheric fissure, and three cortical sulci were measured blindly on computerized tomography (CT) scans of 75 chronic psychiatric patients and 62 asymptomatic volunteers, all less than 50 years of age. A total of 19 of the 60 patients with chronic schizophrenia had at least one abnormality. All 15 patients with other diagnoses were within the control range. Comparing those chronic schizophrenic patients with abnormalities to those without them, there were no significant differences in age, length of illness or treatment, and length of hospitalization. From this and ventricular size data, two thirds of the chronic schizophrenics had some cerebral structural abnormality. Ventricular enlargement did not correlate significantly with cortical abnormalities. Therefore, more than one etiology may account for the structural abnormalities found in chronic schizophrenic patients.     

Sleep quality in patients with chronic renal failure: a 3-year longitudinal study

BACKGROUND: Despite the high prevalence of sleep disorders in patients with kidney disease, no relationship has been demonstrated between sleep quality and the degree of renal function in cross-sectional studies. A prospective trial was, therefore, started in patients with chronic renal failure (CRF) to evaluate whether a link exists between the modifications of these parameters observed during a three-year follow-up period. METHODS: Sleep quality was determined by the Pittsburgh Sleep Quality Index (PSQI) at baseline and after two and three years (Time 0, 2 and 3, respectively) in 78 patients with various degrees of CRF in association with the main clinical and biochemical variables. RESULTS: The baseline PSQI averaged 6.2+/-3.8 (range: 0-21, with higher values indicating worse sleep quality) and was significantly increased at both Time 2 and 3 (8.8+/-3.7 and 10.2+/-3.5, respectively, P<0.0001 vs baseline), whereas creatinine clearance progressively decreased (45+/-24 vs 41+/-26 and 32+/-20ml/min, at time 0, 2 and 3, respectively, P<0.0001), although an independent association with PSQI could not be demonstrated after adjustment for confounding factors (P=0.90, mixed linear model). CONCLUSIONS: Our data suggest that the progression of renal disease is accompanied by a progressive worsening of sleep quality; age is strongly related to both phenomena. PSQI represents an easy tool to use to detect sleep disorders and to more effectively evaluate renal patients; the prevention of sleep disorders by early and appropriate treatments could beneficially influence the course of the disease.     

Frequency of dystrophic muscle abnormalities in chronic progressive external ophthalmoplegia: analysis of 86 patients

BACKGROUND: There are few reports describing the coexistence of dystrophic features with those typical of mitochondrial myopathies in muscle biopsy. A recent study suggested that dystrophic features are frequent in patients with chronic progressive external ophthalmoplegia (CPEO) with a high mutation load, but the actual frequency of these abnormalities in CPEO remains undetermined. OBJECTIVE: To review the occurrence of dystrophic abnormalities in a large series of patients with CPEO to assess the frequency of such abnormalities and to verify whether they are correlated with specific mitochondrial DNA (mtDNA) mutations. METHODS: Retrospective survey of case series (86 patients with CPEO). RESULTS: Only three cases with dystrophic abnormalities were found: two with a large scale mtDNA deletion and one with the A3251G mutation. All three patients showed predominantly proximal muscular weakness resembling limb girdle muscular dystrophy. CONCLUSIONS: Dystrophic abnormalities are rare in CPEO and are not correlated with a specific molecular defect.     

Prefrontal abnormalities in patients with simple schizophrenia: structural and functional brain-imaging studies in five cases

Simple schizophrenia is an uncommon disorder with unknown pathophysiology, and its position in the current diagnostic system is ambiguous. Brain-imaging studies may help to elucidate its pathophysiology. Five patients fulfilling both ICD-10 criteria for simple schizophrenia and DSM-IV criteria for simple deteriorative disorder underwent computed tomography, magnetic resonance imaging, and single photon emission computed tomography. These scans were assessed individually by visual inspection as well as automatically by comparison with scans in normal controls or other schizophrenia subtype patients using voxel-based image analyses. Three of the five simple schizophrenia patients had findings of atrophy and reduced cerebral perfusion in the frontal areas. Voxel-based analyses also showed prefrontal grey matter deficits and hypoperfusion in simple schizophrenia patients compared with the controls. Although this study is limited by the small number of patients with simple schizophrenia, the results suggest that simple schizophrenia, or at least this subpopulation, may have rather homogeneous morphological and functional deficits in the prefrontal cortex. It is also suggested that simple schizophrenia may occupy an extreme position of the schizophrenic continuum where the prefrontal deficits and negative symptoms are most purely manifested.     

A chronic psychotic: a longitudinal perspective

Psychiatric illnesses involve complex interpersonal and biological processes that combine to produce certain clinical signs and symptoms of psychopathology on which psychiatric diagnostics are based. Nevertheless, the clinical presentation of some psychiatric disorders may vary from patient to patient or at different points in time on the same patient. The following case history serves to underscore the importance of the multi-axial approach in combination with longitudinal follow-up when an attempt is made to understand fully complex individuals. In particular, this case involves, at the minimum, the complex interweaving of a psychosis not easily subsumed under either pure schizophrenia or pure affective disorder together with substance abuse. It is the analysis of the serial unfolding of psychopathology that the authors feel will lead to a more comprehensive and better diagnostic formulation of an individual patient.     

Effect of high-dose steroid therapy on T-cell subpopulations A longitudinal study in MS patients

Lymphocyte subpopulations, T cell activation antigens, and serum levels of interleukin 2 (IL-2) and soluble IL-2 receptor (sIL2R), were studied in relapsing-remitting MS (RR-MS) patients before and after high-dose steroid therapy. Prior to therapy, a minority of patients showed increased HLA-DR antigen expression, and an increased number of CD16 + and CD19+ cells. Steroid treatment induced a significant increase in HLA-DR and CD 19 expression, a significant reduction in CD 16 +, CD57 +, and CD8 + CD57 + cells, and a slight, non-significant, decrease in IL-2 and sIL-2R levels and CD25 expression on CD4 + T lymphocytes.