Methamphetamine-Associated Hyperammonemic Encephalopathy

Abstract

M ethamphetamine is a commonly abused psychostimulant drug, causing persistent damage to both dopaminergic and serotonergic systems. 1 Both acute use and chronic use of methamphetamine are often associated with cognitive deficits, ranging from impulse control disorders and impairment in attention, working memory, and decision making to motor incoordination. 2,3 Ammonia (NH3) resulted from the catabolism of amino acid. In healthy individuals, ammonia mainly resulted from the degradation of protein and urea by intestinal bacteria and detoxified in the liver through conversion to urea. The kidney also produces ammonia in proximal tubule, to buffer H+ in the urine. 4 Mild hyperammonemia can cause neuropsychiatric, irritability, headache, vomiting, ataxia, and gait abnormalities, and in severe acute cases, it can lead to rapid progression, often fatal, encephalopathy and cerebral edema. Recently, the relationship between hyperammonemia and methamphetamine intoxication, as well as contributory role of ammonia in methamphetamine-associated mental status changes, has been reported in clinical studies and some animal studies. [5][6][7][8] We report 2 cases of methamphetamineassociated hyperammonemia, who presented with psychiatric manifestation.

Extrahepatic portosystemic shunts as an unusual but treatable cause of hyperammonemic encephalopathy in a noncirrhotic patient – a case report

“… 10 , 11 Furthermore, exposure to various substances has been associated with hyperammonemia, including carbamazepine, ribavirin, methamphetamine and chemotherapeutic agents, such as 5-FU. 12 – 16 While the underlying mechanisms are not well understood in most of these agents, a clearer concept exists for the etiopathogenesis of VPA-induced hyperammonemia. Among many other interactions, VPA disrupts the urea cycle by inhibiting the rate-limiting enzyme (carbamoylphosphate synthetase I) through one of its metabolites (propionic acid).…”

“…10,11 Furthermore, exposure to various substances has been associated with hyperammonemia, including carbamazepine, ribavirin, methamphetamine and chemotherapeutic agents, such as 5-FU. [12][13][14][15][16] While the underlying mechanisms are not well understood in most of these agents, a clearer concept exists for the etiopathogenesis of VPA-induced hyperammonemia.…”

A glance at transient hyperammonemia of the newborn: Pathophysiology, diagnosis, and treatment: A review

“…Portosystemic shunt Carbamoylphosphate synthetase 1 deficiency Infection Ornithine transcarbamylase deficiency Coronavirus disease [16] Argininosuccinate synthetase deficiency Urease-positive bacteria (C. neoformans, Mycoplasma hominis) overgrowth [26,27] Inhibitors of carbonic anhydrases (like topiramate) [28] Carnitine palmitoyltransferase II deficiency Asparaginase Carnitine-acylcarnitine translocase Sunitinib [29] Mitochondrial energy production disorder Methamphetamine [30] Mitochondrial complex V deficiency Nutrition Mitochondrial complex III deficiency Imbalanced total parenteral nutrition Combined oxidative phosphorylation deficiency 5…”

“…As shown in Table 1, THAN is an exclusive diagnosis that can only be made when other known causes of hyperammonemia are excluded. [16,[24][25][26][27][28][29][30] The mechanisms involved in THAN development are controversial. Fortunately, some clues have been derived from well-documented reports.…”

“…[36] When severe systemic infection occurs, platelets adherent to the liver vasculature actively migrate to scan Table 1 The causes of hypermmonemia. [16,[24][25][26][27][28][29][30]…”