Lithium induced reversible Splenial lesion in neuroleptic malignant syndrome like symptoms: two case reports.

BACKGROUND: Lithium is primarily used to treat bipolar disorder and is known to cause several acute neurological complications. Reversible splenial lesions (RSLs) may be evident in antiepileptic drug toxicity or withdrawal, infections, and other phenomena. We report two cases of RSL presenting as neuroleptic malignant syndrome-like symptoms (NMSLS) with lithium associated neurotoxicity. CASE PRESENTATION: A 28-year-old woman was admitted after taking increased dosages of lithium for schizophrenia. She experienced generalized tremor, rigidity, dysarthria, high fever, and tachycardia. Symptoms and brain lesion recovered 2 weeks after discontinuation of lithium. The second case involved a 59-year-old woman who was receiving treatment for bipolar disorder since 1988. When lithium was administered for impatience and aggressive behavior, her mental state deteriorated and fever developed, along with generalized tremor in the extremities. Brain magnetic resonance imaging (MRI) in both patients showed a reversible oval-shaped lesion localized to the splenium of the corpus callosum. Both patients were defined as neuroleptic malignant syndrome-like symptoms (NMSLS) based on the DSM-5 diagnostic criteria for neuroleptic malignant syndrome. The suspected etiology of our cases was lithium associated neurotoxicity according to their clinical course and medical information. Our patients fully recovered in 10-14 days after the discontinuation of lithium. CONCLUSIONS: The patients experienced similar clinical courses and had similar radiological findings of RSL. Manifestations in both cases were related to lithium associated neurotoxicity and this should be considered in patients with RSL and NMSLS.

Reversible magnetic resonance imaging changes in a case of neuroleptic malignant syndrome.

Neuroleptic malignant syndrome (NMS) is a life-threatening neurologic emergency associated with the use of mainly typical antipsychotic drugs. It is characterized by fever, altered mental status, generalized rigidity, autonomic instability, myoclonus, raised creatine phosphokinase, rhabdomyolysis, and leukocytosis. Neuroimaging (brain computed tomography/magnetic resonance imaging [MRI]) is usually normal in most of the cases of NMS. Magnetic resonance imaging findings have not been well elucidated in NMS as yet. Very few cases have been reported worldwide. We herein, report a case of a 42-year-old patient of NMS, who presented to us with reversible changes in MRI brain. This case report highlights the possible MRI changes in NMS and their plausible mechanism.

A Reversible Isolated Lesion in the Splenium of Corpus Callosum in a Patient with Probable Neuroleptic Malignant Syndrome -- Case Report.

PURPOSE: A reversible isolated lesion in the splenium of the corpus callosum (SCC) is rare. We present such a case in a young female patient with neuroleptic malignant syndrome (NMS) and elaborate on its proposed pathophysiology and the possible differential diagnoses. CASE REPORT: A 28-year-old female was on neuropsychiatric treatment (clozapine) for schizoaffective disorder. NMS was diagnosed based on the clinical presentation of fever, mental status change (with disorientation and visual hallucination), generalized muscular rigidity (catatonic signs), tremor, and markedly increased creatine phosphokinase (1824 U/l) after 10-day administration of clozapine. The SCC lesion had a "boomerang" appearance and high signal intensity on the initial T2-weighted, T2 fluid attenuated inversion recovery, and diffusion-weighted magnetic resonance images, and decreased apparent diffusion coefficient values. The follow-up magnetic resonance imaging 12 weeks later showed complete resolution of the SCC lesion. CONCLUSION: A reversible isolated SCC lesion is a distinct clinicoradiological syndrome of varied etiology. The changes may occur in certain psychiatric patients with NMS and most patients with epilepsy and encephalitis. The etiological mechanism remains uncertain and enigmatic, but the neurological course and outcome are good.

Reversible abnormality of the splenium in a bipolar patient with neuroleptic malignant syndrome.

OBJECTIVE: To report reversible abnormality of the splenium in a bipolar patient with neuroleptic malignant syndrome (NMS). METHODS: We studied a 23-year-old male who received oral and parenteral neuroleptics, atypical antipsychotic agents, and mood stabilizers, as well as a course of six electroconvulsive therapy treatments, for an episode of mania. He improved. Five days after discharge on maintenance atypical antipsychotic agents and mood stabilizers, he returned with symptoms suggestive of NMS. Laboratory investigations revealed leucopenia, thrombocytopenia, and elevated creatine phosphokinase levels. Brain magnetic resonance imaging showed swelling of the splenium with centrally restricted diffusion; there was no other abnormality. He was defensively treated with antimicrobials, methylprednisolone, and bromocriptine. RESULTS: Clinical recovery was complete after nine days, and the splenium lesion resolved after four further days; there were no neuropsychiatric sequelae. Nine months later, the patient remains well on maintenance lithium therapy. CONCLUSIONS: This is the first report of an isolated splenial lesion reversing within days of resolution of NMS. The outcome supports the recent literature which suggests that an isolated splenial lesion does not need investigation, and that prognosis depends on the underlying disorder, and not on the presence or absence of the splenial lesion.

Lethal neuroleptic malignant syndrome due to amisulpride.

A 42-year old-man was found lying in his bed having seizures. Later he became unconscious and hypotonic developing mydriasis as well as rigidity. The body core temperature (rectal temperature) was above 42 °C. Blood pH was decreased during treatment, and his general condition deteriorated. The patient developed gasping respiration, ventricular fibrillation, and died. During autopsy and histological investigation cerebral and pulmonary edema were noted together with general congestion of the internal organs. Further observations included contraction bands of myocytes, a contracted spleen, fibrosis of the liver, and gall stones. Toxicological analyses of peripheral blood revealed the following results: amisulpride 4.65 mg/l, biperiden 0.12 mg/l, imipramine 0.33 mg/l, and desipramine 0.68 mg/l. An amisulpride-induced neuroleptic malignant syndrome was therefore diagnosed as the patho-physiological mechanism leading to death.

The neuroleptic malignant syndrome: a report of 14 cases from North India.

Neuroleptic malignant syndrome (NMS) is a rare, life-threatening but potentially treatable condition. This study was performed to investigate the clinical spectrum, antecedent events and outcome of NMS patients admitted in the Neurology department of a large teaching hospital of North India. Fourteen cases of NMS were taken after a thorough search during a three-year period (May 2000 to April 2003). The Incidence of NMS was 1.40/ 1000 patients treated with neuroleptics and mortality rate was 14.28%. Amongst the neuroleptics Haloperidol (parenteral) was implicated as a most common drug for NMS in 57% of patients. An association with coexisting precipitating illness was clearly recorded in 71.4% patients. All the recorded patients of NMS received 500-700 mg CPZ equivalent/day of neuroleptics. NMS as an indiosyncratic phenomenon was noticed in 28% patients. 85.7% responded to dopaminergic drugs along with supportive treatment and showed partial or complete recovery within 7-14 days. In those with partial recovery residual deficits included Parkinsonian features, depression and diaphoresis in a small percentage of patients.

"Brief" Aripiprazole-induced Neuroleptic Malignant Syndrome with Symptoms that Only Lasted a Few Hours.

Neuroleptic malignant syndrome (NMS) with characteristic symptoms is a potentially lethal reaction to antipsychotic drugs. Atypical NMS usually lacks major symptoms and frequently occurs after treatment using atypical antipsychotics, such as aripiprazole. A 64-year-old man developed aripiprazole-induced NMS after surgery, and our early recognition of the NMS was based on high creatine kinase levels and low serum iron levels. His characteristic symptoms (a fever, rigidity, and altered mental status) were only present for a few hours and were resolved by aripiprazole discontinuation and supportive care. Aripiprazole-induced NMS can present with brief but major symptoms, and clinicians may overlook this "brief" appearance of NMS.

[The life threatening adverse effects of psychotropic drugs: a case report]. / Psikotrop Ilaçlarin Yasami Tehdit Eden Yan Etkileri: Olgu Sunumu.

Neuroleptic malignant syndrome (NMS) is a rare idiosyncratic reaction to antipsychotic drugs that is potentially fatal. Characteristic features of NMS are hyperthermia, muscular rigidity, severe autonomic dysregulation and disturbed consciousness. Signs and symptoms of serotonin syndrome (SS) can be grouped into four inclusive categories that are almost identical to those of NMS. Clinically, NMS and SS share many features, suggesting different spectrums of a similar disorder. To make a distinction between the two is often difficult because of a large clinical overlap. We present a case of a 42-year-old male with a history of schizophrenia that developed signs and symptoms inconsistent with either NMS or SS after intramuscular administration of 2 typical antipsychotics along with 1 dose of a selective serotonin reuptake inhibitor (SSRI). The patient abruptly developed the clinical features in just 24 h. The patient presented with altered mental status and increased levels of creatinine phosphokinase. Twelve days of intensive care unit treatment was chiefly supportive and included bromocriptine. The final outcome was positive with complete disappearance of the symptoms. The treatment for both NMS and SS is similar. The therapeutic interventions primarily consist of removing the suspected agent and providing supportive care. We present this case to highlight some controversial issues concerning the life threatening adverse effects of psychotropic drugs, which illustrate the spectrum concept.

Dopamine transporter single-photon emission computerized tomography supports diagnosis of akinetic crisis of parkinsonism and of neuroleptic malignant syndrome.

Akinetic crisis (AC) is akin to neuroleptic malignant syndrome (NMS) and is the most severe and possibly lethal complication of parkinsonism. Diagnosis is today based only on clinical assessments yet is often marred by concomitant precipitating factors. Our purpose is to evidence that AC and NMS can be reliably evidenced by FP/CIT single-photon emission computerized tomography (SPECT) performed during the crisis. Prospective cohort evaluation in 6 patients. In 5 patients, affected by Parkinson disease or Lewy body dementia, the crisis was categorized as AC. One was diagnosed as having NMS because of exposure to risperidone. In all FP/CIT, SPECT was performed in the acute phase. SPECT was repeated 3 to 6 months after the acute event in 5 patients. Visual assessments and semiquantitative evaluations of binding potentials (BPs) were used. To exclude the interference of emergency treatments, FP/CIT BP was also evaluated in 4 patients currently treated with apomorphine. During AC or NMS, BP values in caudate and putamen were reduced by 95% to 80%, to noise level with a nearly complete loss of striatum dopamine transporter-binding, corresponding to the "burst striatum" pattern. The follow-up re-evaluation in surviving patients showed a recovery of values to the range expected for Parkinsonisms of same disease duration. No binding effects of apomorphine were observed. By showing the outstanding binding reduction, presynaptic dopamine transporter ligand can provide instrumental evidence of AC in Parkinsonism and NMS.

Hypothalamic pathology in the neuroleptic malignant syndrome.

The pathogenesis of the neuroleptic malignant syndrome is currently unclear, and no specific morphological abnormalities in the CNS of victims of neuroleptic malignant syndrome have been described. The authors report a case of neuroleptic malignant syndrome with recent foci of necrosis in the anterior and lateral hypothalamic nuclei. They discuss the role of tricyclic antidepressants, monoamine oxidase inhibitors, and neuroleptics in the development of this syndrome. They conclude that although the pathogenesis of the neuroleptic malignant syndrome is still not clear, necrosis of the hypothalamic nuclei may be pathognomonic for this syndrome.

Brain neurotransmitter changes in three patients who had a fatal hyperthermia syndrome.

The authors examined the autopsied brains from three patients who had a fatal hyperthermia syndrome. There was marked hypothalamic noradrenaline depletion in all three patients, severe brain choline acetyltransferase deficiency with nucleus basalis cell loss in two patients, and mild to moderate brain choline acetyltransferase loss in one patient. Striatal dopamine metabolite/dopamine ratio was below normal in two patients and not elevated, as would be expected after short-term neuroleptic administration, in the third. This suggests that reduced capability (aggravated by the cholinergic deficit) of the nigrostriatal dopamine system to respond adequately to stress and/or neuroleptic-induced receptor blockade may be important in the development and course of fatal hyperthermia syndrome.

Neuroleptic malignant syndrome: caffeine contracture of single muscle fibers and muscle pathology.

The neuroleptic malignant syndrome (NMS) is similar to anesthesia-induced malignant hyperthermia (MH) in three major clinical features: hyperthermia, muscular rigidity, and myoglobinuria. In eight cases of NMS, we studied caffeine contracture of single skinned muscle fibers. Sensitivity of the sarcoplasmic reticulum to caffeine was abnormally increased in six of the eight cases. Morphologic studies showed type 2B fiber atrophy in all six cases examined, and there were necrotic fibers in two cases. Since skeletal muscle is affected in NMS, these patients may be susceptible to MH.

Fatal hyperthermia in a quadriplegic man. Possible evidence for a peripheral action of haloperidol in neuroleptic malignant syndrome.

A patient with a cervical cord transection isolating his hypothalamic thermoregulatory centers from peripheral effectors suffered a fatal hyperthermic episode after receiving haloperidol. This suggests that neuroleptic malignant syndrome is caused by a peripheral, not central, effect of haloperidol.

Acute cardiac failure in neuroleptic malignant syndrome.

We present a case of rapid onset acute cardiac failure developing as part of neuroleptic malignant syndrome in a 35-year-old woman following treatment with thioridazine and lithium. Post mortem histology of cardiac and skeletal muscle showed similar changes of focal cellular necrosis and vacuolation suggesting a common disease process.

Muscle changes in the neuroleptic malignant syndrome.

AIMS: To characterise the skeletal muscle changes in the neuroleptic malignant syndrome (NMS). METHODS: Detailed light and ultrastructural examination was carried out on skeletal muscle from three cases of NMS, two associated with recreational drugs (3,4-methlenedioxymethylamphetamine (MDMA, Ecstasy) and lysergic acid diethylamide (LSD)) and one with antipsychotic drugs (fluoxetine (Prozac) and remoxipride hydrochloride monohydrate (Roxiam)). RESULTS: The muscles were grossly swollen and oedematous in all cases, in one with such severe local involvement that the diagnosis of sarcoma was considered. On microscopy, there was conspicuous oedema. In some fascicles less than 10% of fibres were affected whereas in others more than 50% were pale and enlarged. There was a spectrum of changes: tiny to large vacuoles replaced most of the sarcoplasm and were associated with necrosis. A striking feature in some fibres was the presence of contraction bands separating segments of oedematous myofibrils. Severe endomysial oedema was also detectable. There was a scanty mononuclear infiltrate but no evidence of regeneration. CONCLUSIONS: The muscle changes associated with NMS are characteristic and may be helpful in differential diagnosis.

Muscle pathology in the neuroleptic malignant syndrome.

In a fatal case of neuroleptic malignant syndrome, a muscle sample taken within 1 h of death showed acute myopathic features with absence of muscle glycogen and neutral lipid. These features suggest that hyperpyrexia in this syndrome may be caused by heat production from uncoupled phosphorylation in muscle and imply that the primary biochemical abnormality responsible for this uncontrolled heat production might be muscular rather than hypothalamic.