Paroxysmal hypothermia (PH) is a rare condition characterized by recurrent episodes of spontaneous hypothermia, bradycardia, disorders of consciousness and, in some cases, hyperhidrosis. When associated with a detectable hypothalamic lesion, PH episodes usually occur shortly after the brain insult.
We performed a retrospective study to identify patients who had demonstrated at least one episode of symptomatic spontaneous PH as defined by (i) tympanic temperature < 35 °C; (ii) drowsiness and/or confusion state and/or coma; (iii) duration of the episode ≥ 24 h; (iv) absence of other condition resulting in hypothermia
Among 8824 patients, we identified four patients with recurrent late-onset PH episodes of 1–26-day duration that occurred 6–46 years after the brain insult. The lesion always involved the diencephalon. All patients suffered from epilepsy and three of hypopituitarism. PH episode typically included severe hypothermia, bradycardia, drowsiness, thrombocytopenia and in some patients central hypoventilation and narcolepsy-like hypersomnia. In ¼ of episodes, confusion was mistaken as non-convulsive epileptic manifestation resulting in benzodiazepine administration which aggravated symptoms. In the two patients with nocturnal hypoventilation, chronic non-invasive ventilation with bi-level positive airway pressure allowed cessation of symptomatic episodes.
Late-onset post-lesional PH is exceptional with only a single case hitherto reported in the literature. Distinguishing hypothermia-related disturbances of consciousness from epileptic seizures or post-ictal phenomena is crucial since treatment with benzodiazepines may worsen hypothermia through their action on GABAa receptors. Lastly, PH may be associated with sleep disorders and hypoventilation, for which investigations and treatment should be considered.
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Shapiro WR, Williams GH, Plum F (1969) Spontaneous recurrent hypothermia accompanying agenesis of the corpus callosum. Brain 92:423–436
Benarroch EE (2007) Thermoregulation: recent concepts and remaining questions. Neurology 69:1293–1297
Tambasco N, Belcastro V, Prontera P, Nigro P, Donti E, Rossi A et al (2014) Shapiro’s syndrome: defining the clinical spectrum of the spontaneous paroxysmal hypothermia syndrome. Eur J Paediatr Neurol 18:453–457
Ruiz C, Gener B, Garaizar C, Prats JM (2003) Episodic spontaneous hypothermia: a periodic childhood syndrome. Pediatr Neurol 28:304–306
Johnson NC, Morgan MW (2006) An unusual case of 4-aminopyridine toxicity. J Emerg Med 30:175–177
Alty JE, Ford HL (2008) Multi-system complications of hypothermia: a case of recurrent episodic hypothermia with a review of the pathophysiology of hypothermia. Postgrad Med J 84:282–286
Darlix A, Mathey G, Sauvée M, Braun M, Debouverie M (2012) Paroxysmal hypothermia in two patients with multiple sclerosis. Eur Neurol 67:268–271
Edwards S, Lennox G, Robson K, Whiteley A (1996) Hypothermia due to hypothalamic involvement in multiple sclerosis. J Neurol Neurosurg Psychiatr 61:419–420
Ghawche F, Destée A (1990) Hypothermia and multiple sclerosis. A case with 3 episodes of transient hypothermia. Rev Neurol (Paris) 146:767–769
Lammens M, Lissoir F, Carton H (1989) Hypothermia in three patients with multiple sclerosis. Clin Neurol Neurosurg 91:117–121
Linker RA, Mohr A, Cepek L, Gold R, Prange H (2006) Core hypothermia in multiple sclerosis: case report with magnetic resonance imaging localization of a thalamic lesion. Mult Scler 12:112–115
Weiss N, Hasboun D, Demeret S, Fontaine B, Bolgert F, Lyon-Caen O et al (2009) Paroxysmal hypothermia as a clinical feature of multiple sclerosis. Neurology 72:193–195
White KD, Scoones DJ, Newman PK (1996) Hypothermia in multiple sclerosis. J Neurol Neurosurg Psychiatr 61:369–375
Vinetti M, Duprez T, Lawson TM, Vanthuyne V, Hantson P (2015) Spontaneous periodic hypothermia in the postoperative phase of a brain tumor of the third ventricle. Acta Neurol Belg 115:753–755
Milhaud D, Thouvenot E, Heroum C, Escuret E (2005) Prolonged moderate hypothermia in massive hemispheric infarction: clinical experience. J Neurosurg Anesthesiol 17:49–53
De Tanti A, Gasperini G, Rossini M (2005) Paroxysmal episodic hypothalamic instability with hypothermia after traumatic brain injury. Brain Inj 19:1277–1283
Darnell RB, Arbit E (1993) Reversible diencephalic dysfunction: episodic hyperhidrosis due to a trapped third ventricle. Neurology 43:579–582
Tuettenberg J, Woitzik J, Siegel L, Thomé C (2003) Episodic hypothermia and hyperhidrosis after subarachnoid haemorrhage. Case illustration. J Neurosurg 99:610
Moulignier A, Guiard-Schmid JB, Gbadoe AH, Rozenbaum W (2003) HIV-1-related spontaneous episodic hypothermia. Neurology 61:418–419
Okechukwu CN, Pesanti E (1999) Episodic spontaneous hyperhidrosis hypothermia in human immunodeficiency virus-positive patients. Clin Infect Dis 29:210
Fukushima K, Yasaki M, Kaneko K, Fushimi T, Yamamoto K, Hashimoto T et al (2005) Nonparaneoplastic, nonherpetic limbic encephalitis with severe episodic hypothermia: a case report. Eur Neurol 54:170–174
Jacob S, Irani SR, Rajabally YA, Grubneac A, Walters RJ, Yazaki M et al (2008) Hypothermia in VGKC antibody-associated limbic encephalitis. J Neurol Neurosurg Psychiatr 79:202–204
Morrison SF, Nakamura K (2011) Central neural pathways for thermoregulation. Front Biosci (Landmark Ed) 16:74–104
Nakamura K, Morrison SF (2008) A thermosensory pathway that controls body temperature. Nat Neurosci 11:62–71
Hemelsoet DM, De Bleecker JL (2007) Post-traumatic spontaneous recurrent hypothermia: a variant of Shapiro’s syndrome. Eur J Neurol 14:224–227
Pazderska A, O’Connell M, Pender N, Gavin C, Murray B, O’Dowd S (2013) Insights into thermoregulation: a clinico-radiological description of Shapiro syndrome. J Neurol Sci 329:66–68
Vella MA, Jenner C, Betteridge DJ, Jowett NI (1988) Hypothermia-induced thrombocytopenia. J R Soc Med 81:228–229
Ting JY, Manhas D, Innis SM, Albersheim S (2014) Elevated triglycerides levels in two infants with hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia and receiving parenteral nutrition. JPEN J Parenter Enteral Nutr 38:758–760
Ura H, Asai Y, Mori K, Nara S, Yoshida M, Itoh Y (2002) Total necrosis of the pancreas and renal cortex secondary to hypothermia therapy. J Trauma 52:987–989
Villalobos TJ, Adelson E, Riley PA, Crosby WH (1958) A cause of the thrombocytopenia and leukopenia that occur in dogs during deep hypothermia. J Clin Invest 37:1–7
Easterbrook PJ, Davis HP (1985) Thrombocytopenia in hypothermia: a common but poorly recognised complication. Br Med J (Clin Res Ed) 291:23
Wang CH, Chen NC, Tsai MS, Yu PH, Wang AY, Chang WT et al (2015) Therapeutic hypothermia and the risk of hemorrhage: a systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore) 94:e2152
Greenberg RA, Rittichier KK (2003) Pediatric nonenvironmental hypothermia presenting to the emergency department: episodic spontaneous hypothermia with hyperhidrosis. Pediatr Emerg Care 19:32–34
Pineda M, Gonzalez A, Fàbregues I, Fernández-Alvarez E, Ferrer I (1984) Familial agenesis of the corpus callosum with hypothermia and apneic spells. Neuropediatrics 15:63–67
Proulx F, Weber ML, Collu R, Lelièvre M, Larbrisseau A, Delisle M (1993) Hypothalamic dysfunction in a child: a distinct syndrome? Report of a case and review of the literature. Eur J Pediatr 152:526–529
Guyenet PG, Bayliss DA (2015) Neural control of breathing and CO2 homeostasis. Neuron 87:946–961
Eckert DJ, Jordan AS, Merchia P, Malhotra A (2007) Central sleep apnea: pathophysiology and treatment. Chest 131:595–607
de Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE et al (1998) The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci USA 95:322–327
Penfied W (1929) Diencephalic autonomic epilepsy. Arch Neurol Psychiatr 22:358–374
Penfied W (1934) The influence of the diencephalon and hypophysis upon general autonomic function. Can Med Assoc J 30:589–598
Fox RH, Wilkins DC, Bell JA, Bradley RD, Browse NL, Cranston WI et al (1973) Spontaneous periodic hypothermia: diencephalic epilepsy. Br Med J 2:693–695
Dundar NO, Boz A, Duman O, Aydin F, Haspolat S (2008) Spontaneous periodic hypothermia and hyperhidrosis. Pediatr Neurol 39:438–440
Irvine RE (1966) Hypothermia due to diazepam. Br Med J 2:1007
DiFazio MP, Lavenstein B, Demarest S (2014) Profound hypothermia secondary to clobazam use in epilepsy: a novel association. Neurosci Med 5:15–19
Gauthier AC, Quraishi IH, Mattson RH (2016) Hypothermia associated with clobazam use in adult epilepsy. Epilepsy Behav Case Rep 5:17–18
Sankar R (2012) GABA(A) receptor physiology and its relationship to the mechanism of action of the 1,5-benzodiazepine clobazam. CNS Drugs 26:229–244
Conflicts of interest
None of the authors reports disclosure related to the study.
The study complied with the French law about monocentre retrospective analysis of medical data.
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Devic, P., Peter-Derex, L., Richard-Mornas, A. et al. Late-onset post-lesional paroxysmal hypothermia: a case series and literature review. J Neurol (2020). https://doi.org/10.1007/s00415-020-10013-3
- Paroxysmal hypothermia
- Hypothalamus lesions