A case of disseminated microscopic demyelination with multifocal dystrophic calcification

We present a 47-year-old woman with a 10-year disease course consisting of episodic confusion, aphasia, psychosis, depression, migrainous headaches and seizures. There was mild elevation of protein levels in the cerebrospinal fluid, progressive cerebral atrophy, and numerous small T1 hypointensities appearing as central “holes” in the corpus callosum on magnetic resonance imaging. She eventually expired due to status epilepticus and subsequent significant respiratory complications. In the central nervous system, there was generalized brain atrophy, and patchy labeling of blood vessels by antibodies to complement component 4d (C4d) and membrane attack complex. Innumerable small patches with loss of cell bodies (neurons and glial cells in gray matter and glial cells in white matter) and demyelination were scattered throughout the brain and spinal cord. There was no cavitation and the passing axons were mostly preserved. Large solid calcified foci were present predominantly in the pons along with disseminated focal calcification involving neuron cell bodies, neurites, and capillaries. Patchy labeling of glial cells and linear structures suggestive of myelin sheaths with C4d antibodies was observed while immunostains for SV40, tau, β-amyloid, alpha synuclein, p62, and trans-activation response DNA-binding protein 43 kDa were negative. Whole-exome sequencing did not reveal any clinically significant variants. Although the radiological findings are suggestive of Susacʼs syndrome (a rare condition characterized by encephalopathy, hearing loss, and branch retinal artery occlusion), in the absence of audiovisual manifestations, a definitive diagnosis cannot be rendered and therefore, this case may be representing a new entity. Further reports of similar cases are needed for clarification.     

Atypical forms of the osmotic demyelination syndrome

Osmotic demyelination syndrome (ODS) is the damage over the central nervous system caused by several electrolytes, metabolic and toxic disorders. We aimed to describe cases of unusual forms of ODS. In a 9-year period, 25 consecutive patients with ODS (15 men; mean age 42 years) were registered in our referral institution, among them, four (16 %) with atypical neuroimaging findings were abstracted for this communication. None of them presented cardiorespiratory arrest, head trauma, seizures, neuromyelitis optica spectrum or contact with toxic chemicals. Case 1 was a 33-year-old alcoholic man without hypertension or electrolyte imbalance, who presented a classic central pontine myelinolysis (CPM) and a hemorrhage within the pons. Case 2 was a 34-year-old alcoholic man with hypoglycemia and hyponatremia who presented CPM and diffuse bihemispheric extrapontine myelinolysis (EPM) after correction of serum sodium. Case 3 was a 52-year-old woman with mild hypokalemia and hyponatremia (inadequately corrected), who presented a peduncular and cerebellar EPM. Case 4 was a 67-year-old woman who had a suicidal attempt with antidepressants and carbamazepine without impaired consciousness, who complicated with mild hyponatremia associated with a classical CPM and a spinal cord EPM. Case 2 died and the rest remained with variable neurological impairments at last follow-up visit. With modern neuroimaging, the so-called atypical forms of ODS may not be as rare as previously thought; however, they could have a more adverse outcome than the classical ODS.     

Atypical form of non-Langerhans histiocytosis with disseminated brain and leptomeningeal lesions

An 18 year old girl presented with acute visual loss. T2 weighted brain MRI showed areas of hyperintensities in the thalamic nuclei, internal capsule, lentiform nuclei, the subarachnoidal spaces, and a retrobulbar infiltration. Analysis of CSF showed numerous foamy histiocytes without malignant cells, raised protein, and depressed glucose concentration. Biopsy of the right thalamus demonstrated aggregates of histiocytes with immunohistological and ultrastructural characteristics of non-Langerhans cell histiocytosis. The patient improved with chemotherapy and corticosteroids. After 3 months of treatment, CSF analysis showed no more histiocytes. Cytological examination of CSF can be helpful for the management of patients with extensive histiocytic infiltration.     

Atypical facial pain as a defense against psychosis.

The author describes three women who presented psychotic symptoms 24--48 hours before scheduled neurosurgical procedures for atypical facial pain; all had had extensive dental reconstruction and attempted nerve blocks with no relief. Psychiatric hospitalization and administration of major tranquilizers resulted in control of symptoms and relief of pain. Two patients were followed for a year and have had return of psychiatric symptoms or facial pain; both have been maintained on medication and have returned to normal activities. The author suggests that the facial pain may have served as a defense against the emergence of psychosis.     

Large subpial plaques of demyelination in a new form of chronic experimental allergic encephalomyelitis in the guinea pig

The current report describes a new technique for producing chronic experimental allergic encephalomyelitis (EAE) accompanied by demyelination in adult strain 13 guinea pigs. The disease is induced by a combination of passive transfer of lymph node cells sensitized to myelin basic protein (BP) and active challenge of the recipients with homologous spinal cord in Freund’s complete adjuvants. The clinical-pathologic spectrum ranges from a progressively fatal form of chronic EAE leading to death in 4–7 wk, through a remitting-relapsing form, to a chronic-stable form lasting many months. In all of these forms large subpial plaques of demyelination occur in the spinal cord with active phagocytosis of myelin debris, especially at the edges. The axons are swollen, but remain intact throughout. The histologic appearances of the lesions suggest that lysis of myelin occurs before phagocytosis, one of the hypotheses proposed for the pathogenesis of lesions occurring in humans with multiple sclerosis.     

Atypical presentations of acute disseminated encephalomyelitis (ADEM) in HIV infection

Acute disseminated encephalomyelitis is a monophasic demyelinating disorder of the central nervous system associated with various viral infections including HIV infection. We present the findings of seven HIV-infected patients with mild to moderate immunosuppression presenting with atypical features. Four patients had a multiphasic course; three patients had tumefactive lesions, and two patients had corpus callosum lesions. Two patients with the multiphasic course also had tumefactive lesions. Their clinical and radiological findings are presented. Despite the few cases, we propose that the dysimmune process lying between marked immunosuppression (CD4 < 200 cells/μL) and normal CD4 counts (CD4 > 500 cells/μL) might be responsible for these atypical presentations.     

Atypical antipsychotics in the treatment of drug-induced psychosis in Parkinson's disease.

Our experience with atypical antipsychotics in patients with PD is that their motor effects are not predictable. The multiple reports concerning clozapine's beneficial effects on tremor, dystonia, nocturnal akathisia, and dyskinesias all underscore this observation. However, the appearance of even minor degrees of parkinsonism in normal volunteers or schizophrenics should suggest that an antipsychotic will not be well-tolerated in patients with PD. The treatment of PD is probably the most stringent test of a drug's freedom from parkinsonian side effects. The data from trials in schizophrenia concerning parkinsonian effects cannot always be confidently interpreted. Virtually all subjects in these trials have been treated with typical neuroleptics until shortly before study entry. Because the parkinsonian side effects of these drugs may persist for several months, patients may still show declining levels of parkinsonism even when placed on a drug that induces it if this effect is milder than that induced by the pre-study neuroleptic. Depending on the pre-study drug used and the duration of the study, distinguishing placebo from a low-potency neuroleptic may be impossible. Furthermore, the standard measure of parkinsonism in psychiatric studies is the Simpson-Angus scale which is heavily weighted toward rigidity and may underscore bradykinesia, gait, and posture abnormalities. The prolactin response to an antipsychotic drug may turn out to be a good predictor of its freedom from parkinsonian side effects. That would fit with the data presented above of clozapine and quetiapine having less parkinsonian effects, olanzapine having more but variable effects and risperidone being poorly tolerated. With the data presented above, comprising a current review of all reports of the use of atypical antipsychotics in PD that we could locate, we can say little with certainty. The only drug with confirmed benefit without worsening parkinsonism is clozapine. Open-label trials involving over 400 patients and two multicenter, placebo-controlled, double-blind trials have demonstrated that it is effective in treating the psychosis. It improves tremor, does not worsen other motor functions to any significant extent, and is safe at low doses. Limited data provide conflicting information on both risperidone and olanzapine. Quetiapine seems to be well-tolerated with some, but definitely less, worsening of PD motor features than risperidone and olanzapine. Based on the current literature, our personal experience, and anecdotal experience of other PD specialists which we solicited, we will venture our own interpretation and recommendations. We think risperidone is poorly tolerated and should be used only as a last resort; that olanzapine is better than risperidone but will, in a majority of patients with PD, worsen motor function. We are optimistic, but not yet convinced, that quetiapine may prove to be as effective and better tolerated than clozapine. It will not require cumbersome monitoring because it does not induce a blood dyscrasia. We therefore recommend that DP be treated in the following manner. First, the anti-PD medications should be simplified and reduced as much as tolerated. We think, in general, side effects multiply more with increasing numbers of drugs than with drug dose, so that patients are more likely to tolerate a higher dose of levodopa than a lower dose of levodopa combined with other adjunctive anti-PD medications. In reducing anti-PD medications, we recommend tapering and stopping, if necessary, the drugs with the highest risk-to-benefit ratio first. Anticholinergics are stopped first, then selegiline, dopamine agonists, amantadine, and finally COMT inhibitors, which have no psychotomimetic action of their own. Finally, levodopa is reduced. Generally, a point is reached at which the anti-PD medications cannot be reduced without jeopardizing motor function. If psychosis persists at this point, then an antipsychotic is added. (ABS     

Multiple subpial transection in Landau-Kleffner syndrome

We have considered multiple subpial transection (MST) as a treatment option for Landau-Kleffner syndrome (LKS) for the past 6 years. The effect of this technique on language and cognitive ability, behaviour, seizures, and EEG abnormalities is analysed here. Five children (4 males, 1 female; aged 5.5 to 10 years) underwent MST with sufficiently detailed pre- and postoperative data for analysis. Behaviour and seizure frequency improved dramatically after surgery in all children. Improvement in language also occurred in all children, although none improved to an age-appropriate level. All five had electrical status epilepticus in sleep (ESES) before surgery, which was eliminated by the procedure. One child has had an extension of his MST due to the recurrence of ESES and accompanying clinical deterioration with good effect. An attempt is made to set the effect of MST against the natural history of the condition. MST is an important treatment modality in LKS, although the timing of this intervention and its effect on final language outcome remains to be defined.     

Multiple subpial transections: the Yale experience

PURPOSE: Although resection of an epileptogenic region is the mainstay of epilepsy surgery, epileptogenic areas in functionally critical cortex cannot be approached in that manner. Multiple subpial transection (MST) was developed to treat those refractory seizures without causing unacceptable neurologic deficit. We review our experience with this technique. METHODS: Twelve patients who underwent MST with or without resection between 1990 and 1998 were retrospectively reviewed with regard to seizure and neurologic outcome, and predictive factors. RESULTS: Five (42%) of 12 patients obtained a significant improvement in seizure frequency, and two other patients had a marked decrease in the severity of their seizures. Resection with MST reduced seizure frequency more, but this was not a significant difference. No predictive factors for outcome were identified. Only one patient sustained any persistent neurologic deficit. CONCLUSIONS: In selected patients, MST may be a viable alternative when the epileptogenic focus lies in unresectable cortex. A multicenter study with appreciable patient numbers will be necessary to define predictive factors for success.