An autopsy case of cerebellar degeneration following lithium intoxication with neuroleptic malignant syndrome

Abstract

We report a rare case of cerebellar degeneration that was diagnosed at autopsy in a patient who developed lithium intoxication accompanied by neuroleptic malignant syndrome. This 63 year old female, who suffered from manic depressive psychosis, had received lithium bicarbonate at a daily dose of about 1OOOmg for 4 years. She developed a high fever and extrapyramidal symptoms resembling a neuroleptic type of malignant syndrome and died 1 month later. Autopsy revealed an almost complete loss of Purkinje cells with a mild reduction of granule cells in most areas of the cerebellar hemisphere and vermis, except for the tonsil and flocculus, and mild gliosis in the dentate nucleus. In cases of suspected lithium intoxication, one must be alert to the possibility of neuroleptic malignant syndrome and to prevent cerebellar degeneration.

Permanent lithium‐induced cerebellar toxicity: Three cases and review of literature

“…Strikingly, all cases showed similar cerebellar lesions. The cardinal feature was a significant loss of Purkinje cells with sparing of the surrounding basket cells (found in all cases), similar to observations seen in patients with NMS 5, 6, 12. Astrocytosis as well as vacuolization of the white matter and dentate nucleus was seen in some cases.…”

“…However, there appears to be no minimal temperature that can be considered safe. Very high fever alone as seen in NMS has been associated with cerebellar degeneration that appears similar to cases of lithium toxicity 5, 6. Indeed, in 1 of our cases, the initial diagnostic consideration was NMS.…”

“…The medical literature contains few published neuropathological reports of patients with persistent cerebellar symptoms 5–8. Common features in these cases include fever as well as treatment with neuroleptic medications.…”

Pattern of lithium exposure predicts poisoning severity: evaluation of referrals to a regional poisons unit

“…[5][6][7] Clinical manifestations of lithium toxicity effects may lag behind changes in serum lithium concentrations, due at least in part to delayed distribution into tissues. 8 Lithium poisoning is associated with distinctive histological abnormalities in cerebral tissue, [9][10][11][12] and there may be persistent neurological sequelae despite recovery from the acute effects. [13][14][15][16][17][18] Three distinct patterns of lithium toxicity are recognized: 'acute' in patients not previously receiving lithium, 'acute-on-therapeutic' due to acute ingestion in the setting of current lithium treatment, and 'chronic', which arises insidiously due to lithium accumulation.…”

Reversible brain imaging findings with a severe neurological prognosis of neuroleptic malignant syndrome

“…The cerebellum is particularly sensitive to thermal damage because Purkinje cells are believed to be vulnerable to heat [7]. An autopsy study also revealed cerebellar degeneration in patients with NMS [8]. Sustained hyperthermia can cause prolonged neurologic impairment and multi-organ failure; therefore, early active thermoregulation may satisfactorily improve convalescence.…”