Peripheral nerves are pathologically small in cerebellar ataxia neuropathy vestibular areflexia syndrome: a controlled ultrasound study.

BACKGROUND AND PURPOSE: Sensory neuronopathy is a cardinal feature of cerebellar ataxia neuropathy vestibular areflexia syndrome (CANVAS). Having observed that two patients with CANVAS had small median and ulnar nerves on ultrasound, we set out to examine this finding systematically in a cohort of patients with CANVAS, and compare them with both healthy controls and a cohort of patients with axonal neuropathy. We have previously reported preliminary findings in seven of these patients with CANVAS and seven healthy controls. METHODS: We compared the ultrasound cross-sectional area of median, ulnar, sural and tibial nerves of 14 patients with CANVAS with 14 healthy controls and 14 age- and gender-matched patients with acquired primarily axonal neuropathy. We also compared the individual nerve cross-sectional areas of patients with CANVAS and neuropathy with the reference values of our laboratory control population. RESULTS: The nerve cross-sectional area of patients with CANVAS was smaller than that of both the healthy controls and the neuropathy controls, with highly significant differences at most sites (P < 0.001). Conversely, the nerve cross-sectional areas in the upper limb were larger in neuropathy controls than healthy controls (P < 0.05). On individual analysis, the ultrasound abnormality was sufficiently characteristic to be detected in all but one patient with CANVAS. DISCUSSION: Small nerves in CANVAS probably reflect nerve thinning from loss of axons due to ganglion cell loss. This is distinct from the ultrasound findings in axonal neuropathy, in which nerve size was either normal or enlarged. Our findings indicate a diagnostic role for ultrasound in CANVAS sensory neuronopathy and in differentiating neuronopathy from neuropathy.

The development of a scoring system for symphysis pubis dysfunction.

Based on a review of the literature, a questionnaire was developed to create a scoring system for pregnancy-related symphysis pubis dysfunction (SPD) and completed by 150 (100 without SPD and 50 with SPD) peri-partum women. The questionnaire was tested for reliability in a sub-set of 21 women. Symptoms that were significantly associated with SPD were identified and used in a scoring system in order to diagnose patients with SPD. SPD was reported by 12% of patients in the first trimester, 34% in the second trimester and 52% in the third trimester. Significant symptoms in patients with SPD were: pubic bone pain on walking, turning over in bed, climbing stairs, standing on one leg, and previous damage to back or pelvis. Using a score of 1 for each of the above symptoms, a score of 2 and above was considered diagnostic of SPD. There was 1 false positive score. As SPD is a clinical condition with no definitive diagnostic test, there is a need for a scoring system that will allow patients to be assessed in terms of their symptoms. This system has the potential to facilitate screening, diagnosis and management of SPD as well as allow monitoring of the patient and assessment of the success of various interventions.

Symphysis pubis dysfunction: a review of the literature.

A review of the literature revealed a multitude of terms used to describe Symphysis Pubis Dysfunction (SPD). No unambiguous definition was found, rather the condition is described in terms of symptoms and signs. These occur due to the physiological pelvic ligament relaxation and increased joint mobility seen in pregnancy. The severity of symptoms varies from mild discomfort to severely debilitating pain. There appears to be no correlation between the degree of relaxation of the symphysis pubis and the level of pain and disability. Treatment is generally conservative and delivery is curative in the majority by 6 months post-partum. There is a need for standardisation of terminology, an agreed definition of SPD and a reliable means of assessment of the condition. Additionally there is a need for scientific evaluation of different forms of treatment.

MRI changes during water loading in patients with polydipsia and intermittent hyponatremia.

OBJECTIVE: Patients with polydipsia and intermittent hyponatremia have greater ventricle-brain ratios (VBRs) than matched patients without polydipsia and intermittent hyponatremia and normal subjects. Unlike previous studies, this study controlled for the impact of water loading when examining the volume of intracranial structures. METHOD: Under controlled conditions, eight male schizophrenic patients with polydipsia and intermittent hyponatremia were first assigned to either normal fluid intake or oral water loading and then the alternative condition the following day. Magnetic resonance imaging (MRI) volumetric measurements were made with the use of a standardized protocol. RESULTS: During water loading, total VBR and lateral ventricle volume significantly decreased by 13.1% and 12.6%, respectively. A strong association between change in serum sodium concentration and change in VBR was noted across conditions. CONCLUSIONS: These findings indicate that 1) water loading does not account for the diminished brain volume observed in patients with polydipsia and intermittent hyponatremia in previous studies, and 2) hyponatremia can significantly alter brain morphology on MRI.

Polydipsia-hyponatraemia syndrome : epidemiology, clinical features and treatment.

The polydipsia-hyponatraemia syndrome (PHS) occurs in about 5 to 10% of institutionalised, chronically psychotic patients, 80% of whom have schizophrenia. Major clinical features are polydipsia and dilutional hyponatraemia. Complications of PHS include delirium, generalised seizures, coma and death.Nonpharmacological interventions are fluid restriction, diurnal bodyweight monitoring, behavioural approaches, and supplemental oral sodium chloride administration. These interventions require an experienced and dedicated multidisciplinary staff.A number of pharmacological treatments have been assessed for PHS including the combination of lithium and phenytoin, demeclocycline, propranolol, ACE inhibitors, selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors, typical antipsychotic drugs, clozapine and risperidone. Of these agents, the most promising are the combination of lithium and phenytoin, and clozapine.Integrated treatment requires a highly informed multidisciplinary staff, meticulous monitoring of diurnal weight gain and serum sodium level, and careful record keeping. Acute interventions of observation by trained staff, fluid restriction, water-free areas and supplemental sodium chloride administration are based on diurnal weight gain employing a monthly weight chart and a base weight method. Intravenous hypertonic saline is used briefly and administered in a highly controlled manner when patients with PHS present with generalised seizures and coma. Long term strategies include behavioural interventions and the combination of lithium and phenytoin, and clozapine.

Clozapine treatment in polydipsia and intermittent hyponatremia.

BACKGROUND: Recent case reports indicate that clozapine treatment diminishes excessive diurnal weight gain and alleviates hyponatremia observed in some chronically psychotic patients. We examined the influence of clozapine on sodium metabolism and water regulation across a group of patients with the syndrome of polydipsia and intermittent hyponatremia. METHOD: Eleven patients with treatment-resistant DSM-III-R schizophrenia or schizoaffective disorder were studied. Each had a history of repeated diurnal weight gains of greater than 10% with at least one documented bout of hyponatremia in the 6 months before clozapine treatment. We utilized a target weight protocol and serial laboratory measures to compare changes in sodium metabolism and water regulation during 26 weeks of standard antipsychotic medication and 26 weeks of clozapine treatment. RESULTS: Across patients, we found significant improvement in routinely monitored 6 a.m. and 4 p.m. serum sodium, reflecting normalization of sodium metabolism. We also found that the frequency (as reflected by diurnal weight gain), severity (lowest serum sodium), and estimated quantity (calculated urine volume) of polydipsia improved across patients. Improvement in polydipsia and hyponatremia was associated with decreased necessity for monitoring and restrictive interventions, and tended to be associated with psychiatric improvement. CONCLUSION: We found a corrective and stabilizing effect of clozapine on polydipsia and intermittent hyponatremia. Future studies need to examine the relationship of psychiatric improvement and alterations in the regulation of sodium and water physiology to our findings.

Differential effects of neuroleptic and clozapine on polydipsia and intermittent hyponatremia.

Recent reports indicate that clozapine may dramatically decrease both polydipsia and intermittent hyponatremia associated with chronic psychosis. In contrast, there are conflicting reports regarding the impact of standard neuroleptic treatment in this syndrome. We review the relevant literature examining the effects of antipsychotics on the excessive thirst drive and inordinate arginine vasopressin activity observed in patients with water intoxication. Confounding interpretation of the current literature are inconsistent use of diagnostic criteria and treatment outcome measures. If results of preliminary trials is substantiated, clozapine treatment may provide an opportunity to correct methodological problems and provide greater insight into the syndrome of polydipsia and intermittent hyponatremia.

Treatment of severe axial tardive dystonia with clozapine: case report and hypothesis.

We report a patient with severe axial tardive dystonia who has had dramatic improvement for 4 years after treatment with the atypical antipsychotic drug clozapine (625 mg/day). Clozapine differs from conventional neuroleptics in that it has higher affinity for D1 and lower affinity for D2 dopamine receptors than do conventional antipsychotics, which are relatively selective D2 antagonists. We propose that repetitive stimulation of the D1 receptor by endogenous dopamine, resulting in sensitization of the D1-mediated striatal output in the presence of D2 receptor blockade, is a fundamental mechanism mediating tardive dyskinesia, including the dystonic type. According to this hypothesis, it is primarily the D1 antagonist action of clozapine that accounts for its inability to cause tardive dyskinesia as well as its therapeutic effect in tardive dystonia. Regardless of its mechanism of action, the sustained improvement observed in this case suggests that clozapine should be tried in cases of severe refractory tardive dystonia.

Multidisciplinary approach to psychosis, intermittent hyponatremia, and polydipsia.

The syndrome of psychosis, intermittent hyponatremia, and polydipsia (PIP syndrome), seen in the seriously mentally ill, can result in severe biopsychosocial impairment, including an excessive death rate if not identified early. Because of its impact on the health, functioning, and quality of life of the seriously mentally ill patient, all mental health care providers must be aware of the signs and symptoms of PIP syndrome. Physiological, psychological, behavioral, self-care, and social factors all play a role in the manifestation of the syndrome; it follows that a multidisciplinary approach is crucial to ensure early detection, monitoring, and treatment of this problem both in the hospital and in the community. This article explains how we have incorporated the strengths of various disciplinary strategies into a unified treatment model for managing PIP syndrome and its sequelae.

Neuropsychological manifestations of hyponatremia in chronic schizophrenic patients with the syndrome of psychosis, intermittent hyponatremia and polydipsia (PIP).

We examined the neuropsychological sequelae of water intoxication in nine schizophrenic patients with the syndrome of psychosis, intermittent hyponatremia and polydipsia (PIP). Patients were assessed using a standardized test battery on two occasions following laboratory blood work: once during hyponatremia (serum sodium < 130 mmol/l) and once during normonatremia (serum sodium > 136 mmol/l). Results revealed significant deficits during hyponatremia involving complex information processing skills such as mental flexibility and verbal fluency. In contrast, short-term memory was intact and no deficits in sustained attention or visual-motor scanning were observed. Our results underscore the dramatic fluctuations in neuropsychological functioning due to metabolic and osmotic changes during water loading in PIP syndrome patients. In addition, we found that the neuropsychological effects of hyponatremia are remarkably consistent across patients. These complications, if not recognized, are likely to contribute to worsening of psychosis despite appropriate pharmacological treatment while severely limiting patient ability to actively participate in behavioral interventions.

Case report: recurrent pseudocyesis in a male patient with psychosis, intermittent hyponatremia, and polydipsia.

This report describes a case of recurrent pseudocyesis in a man with psychosis, intermittent hyponatremia, and polydipsia. The pseudocyesis was documented on three separate occasions coinciding with bouts of acute hyponatremia and rapid weight gain stemming from ingestion of large amounts of water. In contrast, no pseudocyesis was elicited during intervening normonatremic states. Abdominal distention, neuropsychological deterioration, and worsening of psychosis during acute hyponatremia are considered as contributing factors to the pseudocyesis.

Development and validation of a behavioral observation measure for the syndrome of psychosis, intermittent hyponatremia, and polydipsia.

A behavioral observation scale (Virginia Polydipsia Scale; VPS) for monitoring drinking patterns was developed and its reliability tested during 25 hours of tandem ratings among six patients with the syndrome of psychosis, intermittent hyponatremia, and polydipsia (PIPS). These ratings were compared to those collected from a control group of six psychiatric inpatients who were similarly observed for 25 hours. The scale was subsequently used to assess day-long drinking in a single PIPS patient. Results demonstrated that the VPS can be reliably administered by trained raters and that it clearly differentiates the drinking patterns of PIPS patients from controls. In addition, our findings highlight associations among drinking behaviors, psychiatric functioning and low serum sodium concentration. On balance, these results support using observational measures of drinking behaviors in future studies of PIPS patients.

Behavioral intervention to reduce water intake in the syndrome of psychosis, intermittent hyponatremia, and polydipsia.

We describe a non-intensive behavioral intervention using an A-B design with extended follow-up on an open psychiatric unit to reduce water intake in a 52-year-old man with the syndrome of psychosis, intermittent hyponatremia, and polydipsia. A reinforcement schedule contingent upon weight gain secondary to water intake was employed. Mean diurnal weight gain was 7.1 pounds during a 23-week baseline which dropped to 4.1 pounds following 23 weeks of treatment and at a 1-year follow-up. Estimated fluid consumption dropped from 10 liters to 4 liters daily and incidents of hyponatremia decreased by 62%.

Clozapine-induced weight gain: prevalence and clinical relevance.

OBJECTIVE: The aim of this study was to determine the prevalence and clinical relevance of weight gain during clozapine treatment. Previous reports indicated clinically significant weight gain in 13% to 85% of patients and an average gain of 9.0 to 24.7 lb. METHOD: Twenty-one state hospital patients with treatment-resistant schizophrenia or schizoaffective disorder were weighed weekly for 12 weeks before clozapine treatment and during the first 16 weeks of treatment. Psychiatric symptoms were rated with a modified version of the Brief Psychiatric Rating Scale (BPRS). RESULTS: The mean weight gain for the entire group was 13.9 lb, or 8.9% of body weight. During the 16 weeks of clozapine treatment, 38% of the patients experienced marked weight gains and 29% had moderate weight gains. The improvements in BPRS total score and composite negative symptom score were significantly greater for the eight patients with marked weight gains than for the other 13 patients. CONCLUSIONS: Clozapine's propensity to induce weight gain may relate to the drug's efficacy and/or its unique neuropharmacologic effects. Increased attention to this phenomenon is important because of the morbidity associated with obesity.