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References | Patient details | Disease duration; MS-type; EDSS | Main complaint(s) before admission | Temperature at admission (°C) | Cognitive symptoms at admission | New neurological signs and symptoms | Dysarthria and/or dysphagia | Haematological abnormalities and onset | Hyponatremia and plasma/urinary osmolalities | Neuroimaging and/or autopsy studies | Suspected diagnosis and disease course | Type of hypothermia and (number of hypothermic episodes) |
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[7] | 61 F | NK; NK; NK | Lethargy, anorexia, poor fluid intake | 29.4 | NK | NK | NK | Hb 12.9 g/dl; MCV 84 fl Platelets 19 × 109/l Bone marrow aspirate: erythroid hypoplasia | NK | No | Death | Acute (1) |
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[8] | 41 F | 7 years; NK; EDSS: 7.0 | 3 weeks confusion, apathy | 32.6 | Confusion, Stupor | Marked rigidity in all limbs | No | After 1/52: Anaemia (Hb 7.9 g/dl) Thrombocytopenia (61 × 109/l) | No | Head CT: no abnormality detected | Treated with passive rewarming. Full clinical recovery in 6 days | Chronic: (1) |
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[8] | 52 F | 24 years; NK; EDSS: 8.0 | 3 weeks: confusion, lethargy | 31.0 | Coma | No | No | Thrombocytopenia (50 × 109/l) at admission, peaking after 5 days (28 × 109/l) and anaemia (Hb 7.4 g/dl) | Yes: (Na+ 107 mmol/l) (?SIADH) | No | Treated with steroids, passive rewarming, hypertonic saline, and furosemide. Full clinical recovery in 5 days | Chronic: (1) |
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[9] | 55 F | 24 years; NK; EDSS: 6.0 | 1 week: confusion, lethargy, visual hallucinations | 33.0 | Confusion | Generalised myoclonus neck stiffness | No | 8 days after: pancytopenia Hb 9.2 g/dl, Platelet 80 × 109/l, Leukocytes 2.9 × 109/l | No | Head CT: no abnormality detected Brain autopsy: multiple old plaques at various locations (incl. basal ganglia, corpus callosum, occipital white matter, and right upper cerebellar peduncle). No hypothalamic lesions except some recent axon swellings and cell loss | Developed bronchopneumonia. Treated with antibiotics. Full clinical recovery | Acute: (4) |
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[9] | 55 F | 22 years; NK; NK | 4 weeks: confusion, bradyphrenia, incontinence | NK | NK | Augmented paraparesis | No | No | No | Brain MRI and CT performed after the 2nd admission with hypothermia. Brain MRI and head CT: Important lesions in periventricular and posterior part of corpus callosum No hypothalamic lesions | Developed bronchopneumonia. Treated with antibiotic and passive rewarming. Full clinical recovery. | Acute: (2) |
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[9] | 58 M | 16 years; NK; EDSS: 7.0 | 2 weeks: lethargy, dysarthria, dysphagia | <35 | Memory deficit | Tetraparesis, bilateral central nystagmus | Dysarthria, dysphagia | Thrombocytopenia: 100 × 109/l | No | Brain MRI performed after the 4th admission with hypothermia. Brain MRI: several periventricular plaques. No hypothalamic lesions | Developed bronchopneumonia. Treated with antibiotics and passive rewarming recovered in days. Some motor deterioration remained | Acute: (4) |
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[10] | 52 M | 14 years; NK; NK | Augmented motor deficits | 32.8 | Confusion | Augmented motor paresis | No | No | Yes: (Na+ 114 mEq/l), plasma hyposmolarity (? SIADH) | Brain MRI: No hypothalamic lesions | Treatment with NaCl infusion and fluid restrictions. Hypothermia self-resolved. Clinical full recovery | Acute: (3) |
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[11] | 63 F | 25 years; NK; NK | Visual disturbances, depression paranoid, unable to stand up without help | 32.4 | Confusion | Worsening neurological signs: bilateral Babinski sign, paraparesis, paresthesia, and ataxia in the right arm and mild postural tremor | Dysarthria | Deranged LFTs (ALT and AST mildly raised with hypoalbuminaemia, 31.7 g/l) | No | Brain MRI: diffuse white matter lesions No hypothalamic lesions | Treated with passive rewarming and parenteral thiamine (? Wernicke Encephalopathy) Normothermia in 3 weeks | Acute (1) |
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[11] | 68 F | 32 years; NK; NK | 3 weeks: gait abnormalities, dysarthria | 31.6 | Confusion, drowsiness | Severe paraparesis, bilateral Babinski sign, asterixis, partial right lateral rectus palsy, cerebellar signs | Dysarthria | Severe hypoalbuminaemia (18.9 g/l), decreased folic acid | No | Brain MRI: multiple periventricular lesions. No hypothalamic lesions | Treated with parenteral thiamine (? Wernicke Encephalopathy). Full recovery within 1 month | Acute (1) |
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[12] | 53 F | NK; NK; NK | 5 days: lethargy, dysphagia, dysarthria | 29.0 | Confusion | Spastic tetraparesis with bilateral extensor plantar but depressed reflexes | Dysarthria | Thrombocytopenia: platelets 79 × 109/l Increased APTT ?DIC Raised amylase (321 IU/l) | No. | Brain and spine autopsy: multiple plaques in the brain and spinal cord. A large hypothalamic plaque was found with evidence of current activity and demyelination | Passive rewarming, antibiotics, and atropine. Developed bronchopneumonia, pancreatitis, and died | Acute (1) |
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[13] | 44 F | 10 years; PR-MS; NK | Few days: confusion, disorientation, hallucinations | 33.3 | Confusion | Flaccid paraplegia and cerebellar syndrome (not augmented) | No | No | No | Brain MRI: T2W hyperintensities in the periventricular white matter | Passive rewarming and full clinical recovery within 10 days | NK |
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[14] | 48 M | 5 years; NK; EDSS: 6.0 | 3 weeks: confusion, disorientation, dysarthria deteriorating mobility, drowsiness, cold lower extremities | Initially 36.0 then 31.0 | Stupor | Initially flaccid paraparesis and increased tone in the upper limbs. Deterioration over 48 h. He developed repetitive facial twitching, neck stiffness, left lower motor facial weakness, and decerebrate posturing | Dysarthria | Thrombocytopenia: 27 × 109/l Anaemia: Hb 12.7 g/dl. Increased PT and APTT and low folate | No | CT head: moderate brain atrophy. Previous MRIs had been normal. Brain MRI: after 1st and 2nd admissions with hypothermia: multiple high signals in periventricular white matter. No hypothalamic lesions. Brain autopsy: plaques in periventricular, midbrain, pons, medulla and hypothalamus (incl. posterior hypothalamic nucleus) | Initially treated with IV methylprednisolone for MS relapse, then with antibiotics for ?UTI. Then, passive rewarming. Normothermia after further 48 h. Packed cells, platelets, and plasma proteins transfusion for bleeding. Discharged in 30 days. Residual spastic paraparesis, incoordination, mild upper limb weakness, and sensory deficit after T12 | Acute then chronic: (2) |
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[14] | 59 M | 30 years; NK; EDSS: 7.0 | 4 weeks: increasing fatigue, lethargy, confusion, then drowsiness, dysphagia, and dysarthria | 33.0 | Stupor | NK | Dysphagia, dysarthria | Thrombocytopenia 95 × 109/l | No | NK | Passive rewarming and IV fluids. Normothermia in 36 hours. Paranoid psychosis and confusion, MI and severe LVF. Residual cognitive impairment | Acute (2) |
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[14] | 57 F | 20 years; NK; EDSS: 7.0 | Decreased mobility, lethargy, dysphagia, | 35.0 | Oriented (initially) | Bilateral optic atrophy and absent oculocephalic response, neck stiffness, rigidity, spastic tetraparesis | Dysarthria, dysphagia | Thrombocytopenia. when normothermic (141) then 99 × 109/l. Raised APTT time. Raised platelets antibodies | Yes: (Na+ 130 mmol/l) | Head CT: bilateral periventricular low density lesions | Rewarming, IV fluids and IV methylprednisolone and antibiotics for ?UTI and respiratory infections were given. Normothermia within 24 hours. Full clinical recovery in 4 weeks | Acute: (2) |
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[14] | 64 F | 30 years; NK; EDSS: 9.0 | Deterioration of motor function, speech disturbance, peripheral oedema, fluctuating consciousness | 34.7 | Confusion | Periorbital oedema, augmented tetraparesis, impaired palatal movements | Dysarthria | No | Yes: (Na+ 130 mmol/l) corrected with fluid restriction. Normal plasma and urinary osmolalities | NK | Passive rewarming. Normothermia in 24 hours. Full clinical recovery in 7 days | Acute (1) |
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[14] | 47 F | No previous MS (diagnosed in retrospective); EDSS: 3.0 | Withdrawal and lethargy | 29.0 | Coma | Neck stiffness, generalised hypertonia. After 3 days: bilateral extensor plantar responses, mild paraparesis, optic disc pallor | NK | Thrombocytopenia: 33 × 109/l Anemia: Hb 10.2 | No | Brain MRI: diffuse cortical atrophy, T2W hyperintense periventricular lesions. No hypothalamic lesions | Rewarming. Normothermia in 3 days. Residual physical and cognitive deficits | Acute: (2) |
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[15] | NK F | NK; NK; NK | Motor and cognitive decline | NK | Drowsiness | Augmented flaccid paresis | Dysarthria | Thrombocytopenia | NK | Head CT and brain MRI: No hypothalamic lesions | NK | Chronic with acute episode: (2) |
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[15] | NK F | NK; NK; NK | Motor and cognitive decline | NK | Drowsiness | Augmented flaccid paresis | Dysarthria | Thrombocytopenia | NK | Head CT and brain MRI: No hypothalamic lesions. | NK | Chronic with acute episodes (NK) |
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[16] | 45 F | 28 years; SP- MS; EDSS: 8.0 | 4 weeks: hypothermia (32-33°C), stupor, hypotension, hyponatraemia, and hypoglycaemia | 33.4 | Stupor | No | Dysarthria | Chronic normocytic anaemia. Elevated APTT (61 s). Raised CRP with negative blood cultures. Hypoglycaemia | Yes: (124 mmol/l). ?CSW syndrome | Head CT and brain MRI: known right parietal defect (previous brain abscess), generalised atrophy, periventricular white matter lesions. particularly in the callosum and a hyperintense lesion in the septal region of right thalamus. No hypothalamic lesions | Antibiotics, IV fluids. Initially recovered then further deterioration within a week (33.1°C) stupor and severe hypotension. Within 2 weeks a 3rd episode of hypothermia (31.2°C), bradycardia, and hypotension. She was treated with droxidopa and then discharged once normothermic and stable | Acute: (6) |
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[4] | 61 F | 30 years; SP-MS; NK | Confusion, agitation | 33.9 | Confusion, agitation | No | No | No | No | Brain MRI performed after 3rd hypothermic episode. Periventricular and brain stem plaques were seen with small vessel ischaemia in the ganglionic regions. No hypothalamic involvement | Spontaneous improvement and discharge with a T of 35.2°C | Chronic with acute episodes (6) |
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[17] | 41 M | 7 years; NK; NK | 3 weeks: slurred speech, hypothermia, dysarthria, paranoid delusions, auditory, visual and tactile hallucinations | 30.0 | Confusion then coma | Bilateral facial droop, miosis, paraplegia (also present before), and bilateral upper extremities weakness | Dysarthria | Platelets: 113000/mm3 | No
| Brain MRI: increased overall lesions and new T2W hypothalamic hyperintensity | Passive rewarming. Then antibiotics and respiratory assistance for ?SUO. Full clinical recovery in 6 weeks. Five monthly IV methylprednisolone infusions (1 g/month) | Acute (6) |
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[18] | 39 M | 24 years; SP-MS; EDSS: 6.5 | Few weeks: augmented spasticity, cognitive decline, confusion | 31.0 | Stupor | Spastic tetraparesis | Dysarthria, dysphagia | Thrombocytopenia (75 × 109/l) Leukopenia (0.7 × 109/l) Elevated APTT (37 s) Raised ALT and AST | No | Brain MRI: T2W multiple white matter lesions and atrophy of corpus callosum. Hypothalamic involvement with bilateral nonenhancing preoptic lesions. After 1 year MRI showed no longer signs | Full clinical recovery | NK |
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[18] | 49 M | 32 years; PP-MS; EDSS: 7.5 | Confusion | 32.4 | Psychomotor slowing | Augmented tetraparesis, bilateral pyramidal syndrome, right cerebellar syndrome | Dysarthria, dysphagia
| Thrombocytopenia (79 × 109/l) Raised AST and ALT | No | Brain MRI: T2W white matter lesions. No hypothalamic involvement | Antibiotics for sepsis and 3 steroid injections. Full clinical recovery within days | Acute (1) |
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