Inflammatory myopathies: clinical,diagnostic and therapeutic aspects

The three major forms of immune-mediated inflammatory myopathy are dermatomyositis (DM), polymyositis (PM), and inclusion-body myositis (IBM). They each have distinctive clinical and histopathologic features that allow the clinician to reach a specific diagnosis in most cases. Magnetic resonance imaging is sometimes helpful, particularly if the diagnosis of IBM is suspected but has not been formally evaluated. Myositis-specific antibodies are not helpful diagnostically but may be of prognostic value; most antibodies have low sensitivity. Muscle biopsy is mandatory to confirm the diagnosis of an inflammatory myopathy and to allow unusual varieties such as eosinophilic, granulomatous, and parasitic myositis, and macrophagic myofasciitis, to be recognized. The treatment of the inflammatory myopathies remains largely empirical and relies upon the use of corticosteroids, immunosuppressive agents, and intravenous immunoglobulin, all of which have nonselective effects on the immune system. Further controlled clinical trials are required to evaluate the relative efficacy of the available therapeutic modalities particularly in combinations, and of newer immunosuppressive agents (mycophenolate mofetil and tacrolimus) and cytokine-based therapies for the treatment of resistant cases of DM, PM, and IBM. Improved understanding of the molecular mechanisms of muscle injury in the inflammatory myopathies should lead to the development of more specific forms of immunotherapy for these conditions.     

Posttraumatic headache. Pathophysiology, clinical, diagnostic and therapeutic aspects

Posttraumatic headache (PTHA) is, usually, one of several symptoms of the posttraumatic syndrome and therefore may be accompanied by somatic, psychological or cognitive disturbances. The aetiology of these symptoms in individuals with mild traumatic brain injury or whiplash injury has been a subject of some controversy with explanations ranging from neural damage to malingering. PTHA can resemble a tension-type headache, migrainous or cervicogenic headaches. Post-whiplash headache habitually is a pain radiating from the neck to the forehead, with moderate intensity and benign, but prolonged course. The pathogenesis of PTHA is still not well-known but might share some common headache pathways with primary headaches. In this chapter, we review recent investigations in the pathophysiology of PTHA, review recognised risk factors for a poor outcome and give some recommendations of management. We also discuss the new diagnostic criteria of IHS Classification, 2004, for PTHA and Headache attributed to whiplash.     

Neurocysticercosis: neurologic, pathogenic, diagnostic and therapeutic aspects

Worldwide neurocysticercosis is the most common parasitic infection of the human brain and meninges. Clinical features of the illness vary with the stage of ova infection, but most problems arise when the mature cyst degenerates. Seizures, increased intracranial pressure, and focal neurologic signs then often develop. Computed tomography and magnetic resonance usually demonstrate Cysticercus cellulosae cysts in the brain. A new immunoblot test for antibodies to the cysticercus seems both sensitive and specific. Treatment with praziquantel or albendazole has hastened the disappearance of the cysts on computed tomography and improved clinical symptoms.     

Disturbances of cerebrospinal fluid (CSF) circulation—neuropsychiatrie symptoms and neuroradiological contribution

Summary The present study aimed at relating dementia, pseudo-neurasthenic and affective organic brain syndromes to underlying type of CSF flow disorder and to subsequent alteration of anatomy. T2*-weighted magnetic resonance imaging (MRI) in the midsagittal plane permitted an analysis of aqueductal CSF flow phenomena and hydrocephalus-induced elevation, thinning and dorsal impingement of the corpus callosum. Furthermore, the width of the third ventricle was measured on the transverse scout images. 72 patients with communicating hydrocephalus (increased aqueductal CSF pulsations) and 26 patients with aqueductal stenosis (absence of aqueductal flow phenomena) were compared with 22 controls. Dementia and affective disorders were distributed equally among both CSF flow subgroups whereas pseudo-neurasthenic syndromes were observed more frequently in non-communicating hydrocephalus (p < 0.03). Alzheimer-type and multiinfarct dementia syndromes were found more frequently in communicating hydrocephalus whereas non-classifiable dementia showed some predilection for non-communicating hydrocephalus. Callosal height, area and third ventricular width did not predict affective or pseudoneurasthenic disorder whereas third ventricular width (p < 0.01) and callosal area (p < 0.05) discriminated between demented and non-demented patients. Dorsal impingement of the corpus callosum by the falx was a non-specific finding.     

CSF oxytocin in anorexia nervosa and bulimia nervosa: clinical and pathophysiologic considerations

Oxytocin is a hypothalamic neuropeptide with both centrally and peripherally directed pathways. Data from experimental animals indicate that oxytocin impairs consolidation of aversively conditioned behaviors and is released after feeding or experimental gastric distension. The authors report that the mean CSF oxytocin level of five underweight women with restricting anorexia, but not 12 underweight bulimic anorexic women or 35 normal-weight women with bulimia nervosa, was significantly lower than the level of 11 control subjects. Restricting anorexic patients' low CSF oxytocin levels may reflect their persistently low food intake, and this behavior may exacerbate their tendency for perseverative preoccupation with adverse consequences of food intake.     

Cryptococcal meningitis: clinical, diagnostic and therapeutic overviews

Cryptococcal meningitis has emerged as a leading cause of infectious morbidity and mortality in patients with AIDS. Among the human immunodeficiency virus (HIV)-seropositive subjects, cryptococcal meningitis is the second most common cause of opportunistic neuro-infection. Current trends are changing due to the marked improvement of quality and length of life produced by highly active antiretroviral therapy (HAART). The introduction of generic HAART in India has resulted in an increase in the number of individuals getting treatment for HIV infection, as the cost of highly active antiretroviral therapy (HAART) has decreased 20- fold. Cryptococcal meningitis occurs in non-HIV patients who are immunodeficient due to diabetes, cancer, solid organ transplants, chemotherapeutic drugs, hematological malignancies etc and rarely in healthy individuals with no obvious predisposing factors. Diagnosis of cryptococcal meningitis is fairly straightforward once the diagnosis is considered in the differential diagnosis of chronic meningitis. Treatment of a patient with cryptococcal infection is a challenge for both the physician and the patient, but rewarding, as many would recover with timely and adequate antifungal therapy.     

Focal dystonia: clinical, etiologic and therapeutic aspects

Blepharospasm, spasmodic torticoli, and writer's cramp are the most frequently observed forms of focal dystonia. Primary dystonia is often a hereditary condition with a dominant autosomal mode of transmission and variable penetrance. Secondary conditions are generally the expression of a lesion to the basal ganglia due to an iatrogenic cause or exceptionally the inaugural sign of a metabolic disease. The basal ganglia play an important role in the pathophysiology of this reciprocal innervation disorder but progress in genetics may help better understand the different molecular mechanisms involved. Treatment relies on botulin toxin associated with physical therapy depending on the localization. Drug therapy is often disappointing due to minimal efficacy and poor tolerance.     

Prognostic and therapeutic aspects of catathymis delusions]

The prognostic and therapeutic aspects of catathymic delusional formations, excluding those associated with organic psychoses, are comprehensively presented from five points of view: (1) the present possibilities of psychiatric prognostication; (2) prognostic implications of nosological classifications; (3) prognostic significance of nosographic characteristics; (4) relationship to general rules of psychiatric prognostics; (5) therapautic points. Under (3) we report our own findings concerning the long-term development of delusional formations and the long-term course of delusional illnesses classified as 'schizophrenia of late onset'; we report their relationships to the formation of defect syndromes and to the psycho-organic deterioration in old age.     

A case-study of PTSD in infancy: diagnostic, neurophysiological, developmental and therapeutic aspects

Post-traumatic Stress Disorder of Infancy has become accepted as a nosological entity. Assessment guidelines and diagnostic criteria have been defined, taking into account the impact of development on the expression of post-traumatic symptoms. Therapeutic reenactment has been considered the cornerstone of the therapeutic process. The issue of deciding what is the optimal time for therapist-induced reenactment of the trauma remains ill-defined. The less verbal and the more avoidant the traumatized infant is, the more directive the therapist needs to be, meaning he will not necessarily get clues from the infant of his readiness for reenactment. The therapist will need to introduce the trauma, at the risk of provoking a massive "flight or fight" reaction, as is illustrated by the case study of a two-and-a-half-year-old post-traumatic preverbal boy and his mother. Issues relating to conditions under which reenactment stops causing reactivation of the trauma and starts being a process of therapeutic desensitization are raised. We suggest that integration of psychodynamic and neurodevelopmental concepts might be useful in deepening the understanding of the impact of therapeutic reenactment in PTSD of Infancy.     

Glut-1 deficiency syndrome: clinical, genetic, and therapeutic aspects

Impaired glucose transport across the blood-brain barrier results in Glut-1 deficiency syndrome (Glut-1 DS, OMIM 606777), characterized by infantile seizures, developmental delay, acquired microcephaly, spasticity, ataxia, and hypoglycorrhachia. We studied 16 new Glut-1 deficiency syndrome patients focusing on clinical and laboratory features, molecular genetics, genotype-phenotype correlation, and treatment. These patients were classified phenotypically into three groups. The mean cerebrospinal fluid glucose concentration was 33.1 +/- 4.9mg/dl equal to 37% of the simultaneous blood glucose concentration. The mean cerebrospinal fluid lactate concentration was 1.0 +/- 0.3mM, which was less than the normal mean value of 1.63mM. The mean V(max) for the 3-O-methyl-D-glucose uptake into erythrocytes was 996 fmol/10(6) red blood cells per second, significantly less (54 +/- 11%; t test, p < 0.05) than the mean control value of 1,847. The mean Km value for the patient group (1.4 +/- 0.5mM) was similar to the control group (1.7 +/- 0.5mM; t test, p > 0.05). We identified 16 rearrangements, including seven missense, one nonsense, one insertion, and seven deletion mutations. Fourteen were novel mutations. There were no obvious correlations between phenotype, genotype, or biochemical measures. The ketogenic diet produced good seizure control.     

CSF circulation and blood-CSF barrier.

Results of microzone electrophoresis of non-concentrated CSF after staining with nigrosine and after evaluation on non-transparent acetate film are compared with those of isotope cisternography (111In-DTPA). We found that blood-CSF barrier disturbances begin with an increase of the absolute values of prealbumins in normal CSF circulation. When a barrier impairment occurs, by first increasing the absolute values of alpha1-globulins, we state a pathological CSF circulation. In this case, most of the globulin region is pathologic (globulin-type).     

Dural arteriovenous fistulas with intracranial hemorrhage: diagnostic and therapeutic aspects

Seven patients presented with intracranial hemorrhage due to arteriovenous dural fistula. Six patients showed intracerebral hemorrhage combined with subdural hematoma and intraventricular hemorrhage in one case respectively, and one patient had infratentorial subarachnoid hemorrhage. Location of the fistulae was frontobasal (n=2), tentorium (n=2), transverse sinus (n=2), and superior sagittal sinus (n=1). Angiography revealed reflux into cortical veins in all cases. Therapy was surgery in both cases with fistula of the anterior cranial fossa with good results. An endovascular intraarterial therapy was performed in a case with circumscribed fistula of the superior sagittal sinus, this patient developed a second dural fistula during follow-up. Two patients with tentorial fistulae had primary endovascular treatment complicated by infarction of both thalami in one case and a recurrence of the fistula in the other. In the last case the fistula was closed by surgery. Out of two patients with widespread fistulae of the transverse sinus one made a good clinical recovery and the other remained unchanged. In the first case definite closure of a remnant of the fistula was refused, in the second no further therapy was recommended.