Interictal depression, anxiety, personality traits, and psychological dissociation in patients with temporal lobe epilepsy (TLE) and extra-TLE

PURPOSE: This study was performed to investigate the relation between symptoms of interictal depression, anxiety, personality traits, and psychological dissociation with the localization and lateralization of the epileptogenic zone in patients with partial epilepsy. METHODS: All patients were diagnosed according to the localization-related concept of the 1989 International League Against Epilepsy (ILAE) Classification of Epilepsies and Epileptic Syndromes, and the localization and lateralization of the epileptogenic zone was established by using the clinical criteria for noninvasive presurgical evaluation. This resulted in 67 patients with temporal lobe epilepsy (TLE) and 64 patients with extra-TLE. All patients were assessed on the various aspects of psychopathology by using a comprehensive battery of standardized diagnostic instruments. RESULTS: We did not find the hypothesized excess of psychiatric symptoms in patients with (mesial) TLE in comparison with patients with extra-TLE. We also found no differences between patients with the lateralization of epilepsy in the left versus the right hemisphere. CONCLUSIONS: TLE per se cannot be considered a risk factor in developing more or more severe symptoms of psychopathology in patients with partial epilepsy. Concomitant factors, such as the duration of epilepsy, seizure frequency, and frontal lobe dysfunction may play an additional role. Our findings support the hypothesis of a multifactorial explanation for the psychiatric symptoms in patients with epilepsy.     

Myelin protein zero mutation His39Pro: hereditary motor and sensory neuropathy with variable onset, hearing loss, restless legs and multiple sclerosis

Background

Mutations of myelin protein zero (MPZ) may cause inherited neuropathy with variable expression.

Objective

To report phenotypic variability in a large American kindred with MPZ mutation His39Pro.

Patients

Genetic testing was performed on 77 family members and 200 controls. Clinical and electrophysiological field study assessments were available for review in 47 family members.

Results

His39Pro was found in all 10 individuals prospectively identified with neuropathy. 200 normal controls were without mutation. Symptoms of neuropathy began in adulthood and were slowly progressive except for one acute-onset painful sensory neuropathy. Associated features included premature hearing loss (n  =  7), nocturnal restless leg symptoms (n = 8) and multiple sclerosis in one.

Conclusions

MPZ mutation His39Pro may be associated with acute-onset neuropathy, early‐onset hearing loss and restless legs. The relationship with multiple sclerosis in the proband remains uncertain. Among inherited neuropathies, attempts at correlating phenotype with genotype have met with variable success. Success depends on the specific gene, number of patients studied and the methods by which clinical involvement was ascertained. Of the different genetic causes of hereditary motor and sensory neuropathies, myelin protein zero (MPZ) mutations account for considerable variability, with more than 90 mutations described.¹ Variable degrees of hearing loss,^2,3 pupillary areflexia to light and accommodation,³ and diaphragmatic weakness⁴ or chronic cough⁵ have been reported. Frequent association with restless‐leg‐like symptoms has not been established. The clinical and electrophysiological variability in patients with MPZ mutations may be seen even among monozygotic twins.⁶ Previous studies on families with MPZ mutations were usually carried out on a small number of people. In the kinship reported here, many family members and other controls were studied.On the basis of multiple lines of evidence, changes in immunity represent an attractive potential modifying mechanism for the varied presentations of MPZ mutations.^7,8,9 Rare mutations of the peripheral myelin proteins (PMP22) and connexin 32 have been associated with changes in the central nervous system (CNS) on imaging, characteristic of multiple sclerosis and acute disseminated encephalomyelitis, respectively.^{10,11,12,13,14} In this report, we present data on a large family with the MPZ mutation His39Pro and describe the varied phenotypes seen in the kindred, including one case of acute‐onset painful neuropathy, hearing loss, restless legs and relapsing remitting multiple sclerosis.     

Outpatient psychotherapy for borderline personality disorder: randomized trial of schema-focused therapy vs transference-focused psychotherapy

CONTEXT: Borderline personality disorder is a severe and chronic psychiatric condition, prevalent throughout health care settings. Only limited effects of current treatments have been documented. OBJECTIVE: To compare the effectiveness of schema-focused therapy (SFT) and psychodynamically based transference-focused psychotherapy (TFP) in patients with borderline personality disorder. DESIGN: A multicenter, randomized, 2-group design. SETTING: Four general community mental health centers. PARTICIPANTS: Eighty-eight patients with a Borderline Personality Disorder Severity Index, fourth version, score greater than a predetermined cutoff score. INTERVENTION: Three years of either SFT or TFP with sessions twice a week. MAIN OUTCOME MEASURES: Borderline Personality Disorder Severity Index, fourth version, score; quality of life; general psychopathologic dysfunction; and measures of SFT/TFP personality concepts. Patient assessments were made before randomization and then every 3 months for 3 years. RESULTS: Data on 44 SFT patients and 42 TFP patients were available. The sociodemographic and clinical characteristics of the groups were similar at baseline. Survival analyses revealed a higher dropout risk for TFP patients than for SFT patients (P = .01). Using an intention-to-treat approach, statistically and clinically significant improvements were found for both treatments on all measures after 1-, 2-, and 3-year treatment periods. After 3 years of treatment, survival analyses demonstrated that significantly more SFT patients recovered (relative risk = 2.18; P = .04) or showed reliable clinical improvement (relative risk = 2.33; P = .009) on the Borderline Personality Disorder Severity Index, fourth version. Robust analysis of covariance (ANCOVA) showed that they also improved more in general psychopathologic dysfunction and measures of SFT/TFP personality concepts (P<.001). Finally, SFT patients showed greater increases in quality of life than TFP patients (robust ANCOVAs, P=.03 and P<.001). CONCLUSIONS: Three years of SFT or TFP proved to be effective in reducing borderline personality disorder-specific and general psychopathologic dysfunction and measures of SFT/TFP concepts and in improving quality of life; SFT is more effective than TFP for all measures.     

The natural history and long-term outcome of 57 limb sarcoidosis neuropathy cases

Fifty-seven patients with biopsy-proven sarcoidosis causing limb neuropathy were reviewed in order to delineate the characteristic symptoms, impairments, disability, course, outcome and response to corticosteroid treatment of limb sarcoid neuropathy. Typically the neuropathy had a definite date of symptomatic onset. Prominent were positive neuropathic sensory symptoms (P-NSS), especially pain, overshadowing weakness and sensory loss. P-NSS were the main cause of disability. Almost always the pattern was asymmetric and not length-dependent (unlike distal polyneuropathy). We inferred (from kind and distribution of symptoms, signs and electrophysiologic and other test results) that the pathologic process was focal or multifocal, involving most classes of nerve fibers and variable levels of proximal to distal levels of roots and peripheral nerves. Additional features aiding in diagnosis were: systemic symptoms such as fatigue, malaise, arthralgia, fever and weight loss; involvement of multiple tissues (i.e. skin, lymph nodes and eye); the patterns of neuropathy; MRI features; and ultimately tissue diagnosis. Axonal degeneration predominated, although an acquired demyelinating process was observed in 3 patients. For most cases, the disease had a chronic, monophasic course. MRI studies done in later years of affected neural structures were helpful in identifying leptomeningeal thickening, hilar adenopathy; and enlargement and T2 enhancement of nerve roots, plexuses, and limb nerves. Corticosteroid treatment appeared to ameliorate symptoms more than impairments. Several variables were associated with neuropathic improvement: CSF pleocytosis, short duration between symptom onset and treatment, and a higher grade of disability at first evaluation-a possible rationale for future earlier diagnosis and treatment.     

A novel GABRG2 mutation associated with febrile seizures

Mutations in the gene encoding the gamma2 subunit of the gamma-aminobutyric acid type A receptor (GABRG2) have been reported to cause childhood absence epilepsy (CAE), febrile seizures (FS), and generalized epilepsy with FS plus (GEFS+). The authors analyzed GABRG2 in 47 unrelated patients with CAE, FS, and GEFS+ and identified a novel mutation that cosegregated with FS. Electrophysiologic studies demonstrated altered current desensitization and reduced benzodiazepine enhancement in mutant receptors.     

Reduced expression of synapsin II in a chronic phencyclidine preclinical rat model of schizophrenia

Schizophrenia is a mental disorder characterized by positive symptoms, negative symptoms, and cognitive dysfunction. Phencyclidine (PCP)—a N‐methyl‐D‐aspartate (NMDA) receptor antagonist—induces symptoms indistinguishable from those of schizophrenia. A reduction of the phosphoprotein synapsin II has also been implicated in schizophrenia and has a well‐known role in the maintenance of the presynaptic reserve pool and vesicle mobilization. This study assessed the behavioral and biochemical outcomes of chronic NMDA receptor antagonism in rodents and its implications for the pathophysiology of schizophrenia. Sprague Dawley rats received saline or chronic PCP (5 mg/kg/day) for 14 days via surgically implanted Alzet® osmotic mini‐pumps. Following the treatment period, rats were tested with a series of behavioral paradigms, including locomotor activity, social interaction, and sensorimotor gating. Following behavioral assessment, the medial prefrontal cortex (mPFC) of all rats was isolated for synapsin II protein analysis. Chronic PCP treatment yielded a hyper‐locomotive state (p = 0.0256), reduced social interaction (p = 0.0005), and reduced pre‐pulse inhibition (p < 0.0001) in comparison to saline‐treated controls. Synapsin IIa (p < 0.0001) and IIb (p < 0.0071) levels in the mPFC of chronically treated PCP rats were reduced in comparison to the saline group. Study results confirm that rats subject to chronic PCP treatment display behavioral phenotypes similar to established preclinical animal models of schizophrenia. Reduction of synapsin II expression in this context implicates the role of this protein in the pathophysiology of schizophrenia and sheds light on the longer‐term consequences of NMDA receptor antagonism facilitated by chronic PCP treatment.