Article ID: WMC004512 ISSN 2046-1690

Cough-Induced Transient Global

Peer review status: No

Corresponding Author: Dr. Daniel E Jacome, MD, Dartmouth Hitchcock Medical Center Department of Neurology, One Burnham Street, Suite 2, 01376 - United States of America

Submitting Author: Dr. Daniel E Jacome, MD, Dartmouth Hitchcock Medical Center Department of Neurology, One Burnham Street, Suite 2, 01376 - United States of America

Article ID: WMC004512 Article Type: Case Report Submitted on:09-Jan-2014, 05:40:02 AM GMT Published on: 09-Jan-2014, 06:34:38 AM GMT Article URL: http://www.webmedcentral.com/article_view/4512 Subject Categories:NEUROLOGY Keywords:Amnesia, cough headache,transient global amnesia, transient ischemic attack,epilepsy How to cite the article:Jacome DE. Cough-Induced Transient Global Amnesia. WebmedCentral NEUROLOGY 2014;5(1):WMC004512 Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License(CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Source(s) of Funding: Self funded

Competing Interests: None

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Cough-Induced Transient Global Amnesia

Author(s): Jacome DE

Abstract The overall prognosis of TGA is good. Recurrence rate of TGA is approximately of 22 % in five years, and exceptionally occurs more than twice in a patient lifetime (9). Multiple triggers for TGA have been Two patients developed acute loss of short term identified; from trivial head trauma and sexual activity, memory of several hours duration while preserving to exercise and exposure to cold water (10). autobiographic memory and exhibiting no focal following a crisis of severe coughing. Exceptional patients with acute intracranial bleeding The first patient had recurrent allergic bronchitis; the may present with symptoms of TGA (“secondary second patient had hereditary pressure palsy TGA”).A 68 year old male with acute onset of transient neuropathy (HPPN) secondary to a mutation in the short term memory loss due to an intracranial left PMP 22 gene manifested by protracted cough, frontal hemorrhage was reported by Jacome and eventually ameliorated by the administration of Yanez (11). A temporary disconnection syndrome Levetiracetam. Neither of the two patients had history affecting the basal forebrain-hippocampus pathways of migraine or epilepsy. Imaging studies failed to show was suggested as the potential underlying mechanism. structural or acute vascular lesions on either patient. The Valsalva maneuver has been adduced frequently Symptoms were typical of transient global amnesia as the pathogenic precipitant of TGA resulting from (TGA). Because primary TGA (no lesions apparent on physical and sexual activity, but the development of imaging) may represent a migraine phenomenon TGA following persistent cough has not been singled according to previous reports, I propose that these two out. Although altitudinal TGA, probably mediated by patients exhibited “cough-induced TGA”, precipitated hypoxia and brain edema, has been described before by a similar mechanism causing cough headache but (“Mountain TGA”), the second patient that had TGA presenting as pure confusional migraine, or more while visiting a city in South America located at high formally defined, as “cough-induced persistent altitude, only developed her symptoms following a cognitive migraine aura without .” severe coughing crisis (12). Introduction Case Report(s)

Transient Global Amnesia (TGA) is a condition defined Case One: A 71 year old female was seen in by the abrupt loss of short term memory while neurological consultation a few days after developing preserving autobiographic memory and in the absence acute short term memory impairment without loss of of localizing signs on the neurological examination (1, self-identity and with preservation of automatic 2). Often the patients exhibit repetitive queries. It may behavior, comprehension of language and fluent be confused with transient ischemic attacks (TIAs) or speech. She reported no generalized weakness, with complex partial seizures (2, 3). Current sudoration or with the episode. She understanding on the pathophysiology of non-lesional experienced no . The episode lasted several or "primary TGA" is in support that it represents a hours and was precipitated by a bout of severe migraine phenomenon, even that a good number of persistent dry coughing. She had history of chronic these patients may show subclinical signs of allergic bronchitis, bipolar affective illness-depressive cardiovascular disease (4, 5). It is possible then to type, meralgia paresthesica, right sciatica and infer that TGA often represents “acephalgic” or “acute unilateral restless leg syndrome sometimes interfering confusional migraine” (6). Although an early case with her sleep. She had no cardiac and she study suggested TGA was epileptic in nature, a was hypothyroid. She had no history of epilepsy, subsequent study employing routine and 24 hour EEG migraine or similar episodes of short term amnesia. recordings established the non-epileptic origin of this Her father had polyneuropathy but there were no other disorder in the great majority of cases (3, 7). Yet, in neurological disorders on her family. On neurological the particular patient presenting with acute memory examination she had diminished sensory loss to the emergency room, only an ictal EEG will over the right thigh and brisk reflexes. Head CT scan, establish with certainty the diagnosis of epileptic neck and brain MRA were normal following her amnesia (8).

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memory loss. Her brain MRI showed limited headache may identify those with intracranial posterior non-specific white matter T2 hyperintensities and mild fossa pathology, in other words, as having “secondary cortical atrophy. After nineteen months she has had no cough headache” (14). Of relevance, none of the two recurrent episodes suggestive of TGA. patients herein described suffered from migraine or Case Two: A 68 year old female developed acute reported headache following their transient amnesia. short term memory loss with no other symptoms Persistent cough or coughing crisis may be an lasting for less than 24 hours following a severe exceptional sign of a CNS disorder, i.e., MS or coughing crisis. She reported having no spinocerebellar degeneration (17). lightheadedness, weakness, generalized sweating or a Protracted cough is an unusual manifestation of fainting sensation during the spell. She was visiting La hereditary peripheral neuropathy (18). It is of interest Paz, Bolivia, a city located at high altitude in the Andes that Case 2 had genetically confirmed mutation on the Mountains of South America. She had history of PMP2 gene, probably predisposing her to suffer from chronic dry cough for many years. All her detailed chronic cough, in the absence of alternative cardiopulmonary investigations in the past had been cardiopulmonary explanations. I do not know of a negative. She suffered from ataxia of gait and had left similar occurrence reported previously. leg pain. She had chronic insomnia due to obstructive Rarely premature ventricular contractions (PVCs) sleep apnea and . She had no cardiac precede coughing in exceptional individuals (19). arrhythmia. She had no history of epilepsy or migraine Coughing is triggered by the sudden increase in and no family history of neurological disorders. She pulmonary flow as the result of the stronger reported chronic urinary incontinence, tingling of the ventricular contraction that follows the cardiac pause fingers and mild tremors of the fingers with sustained that allowed previously greater diastolic ventricular action. On neurological examination she exhibited filling. The compensatory increase in blood flow periodic blepharospasm, congenital bilateral stretches the pulmonary artery branches stimulating alternating exotropia, ataxia of gait and areflexia. EEG the vagus nerve cough-inducing sensors, located at three weeks following the incident was normal. Her the vicinity of the main arterial bifurcation (19). brain MRI showed limited non-specific white matter T However, none of the two patients herein described, 2 hyperintensities. The electromyogram (EMG) was had cardiac arrhythmia. normal. Her nerve conduction velocities (NCV) showed evidence of severe axonal polyneuropathy. Diagnostic imaging is indicated in patient with TGA Genetic testing was positive for a mutation on her since rarely TGA may be secondary to brain lesions. PMP-22 gene compatible with Charcot Marie Tooth MRI-MRA findings reported in previous studies in disease type I-A or HPPN. She was prescribed non-lesion cases include delayed abnormal Levetiracetam at a dose of 500 mg b.i.d., with hippocampal hyperintensity in MRI diffusion weighted amelioration of her coughing crisis. In 2 years follow imaging (DWI), and abnormal cerebral venous return, up she reported no further episodes of transient as documented by MRA-TOF (20, 21). According to amnesia. Sedlaczek, et, al, delayed ischemic hippocampal damage is present in most patients with TGA when the Discussion study group is compared with a normal aging population, making TGA not always inconsequential ( 22 ). According to the International Headache Classification As mentioned above, current knowledge favors the 2 (IHC-2- ), cough headache is of sudden onset lasting notion than TGA constitutes a form of migraine at least from seconds to 30 minutes. It is brought on by in a significant number of examples. In a landmark coughing, straining and the Valsalva maneuver (13). publication, Crowell, et al, described 12 patients with Primary and secondary forms (for instance due to headache associated to TGA (4). Four of the twelve posterior fossa tumors or Chari I malformation) are patients had history of migraine. Regional cerebral recognized (13, 14). A malignant form is exceptional, blood flow (rCBF) abnormalities in the study group such as in cases of occult post-surgical sinus CSF consisted of vasomotor responses in the watershed fistula resulting in infectious meningitis (15). It is areas between the middle and the posterior cerebral conceivable that a patient with patent foramen ovale arteries; focal ischemia over the ventral-inferior (PFO) may experience CNS microembolization during temporal lobe was present in five patients of a coughing episodes triggering a behavioral response sub-group of seven subjected to rCBF. These findings simulating confusional migraine and TGA (16). A were atypical for TIA based on CBF criteria, hence, by positive modified Valsalva test in patients with cough

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default, suggestive of a migraine process (4). An amnesia. Clin Electroenceph (1989) 20: 183-192 association between TGA and migraine, mediated by 8. Bilo L, Meo R, Rousi P, de Leva MF, Striano S. stress-induced hippocampus glutamate release Transient epileptic amnesia: an emerging late-onset resulting in cortical spreading depression (CSD), was epileptic syndrome. Epilepsia (2009) 50 (suppl 5) previously proposed by Olesen and Jorgensen (23). 58-61 The pathophysiology of TGA has been normally 9. Hinge HH, Jensen TS, Kjaer M, Marquardsen J, explained on basis on its trigger or underlying Olivarius BdF. The prognosis of transient global disorders, i.e., intracranial bleed, epilepsy or migraine. amnesia. Arch Neurol (1986) 43: 673-676 It is likely than several elements may participate on its 10. Fisher CM. Transient global amnesia. Arch Neurol appearance, since these elements are not mutually (1982) 39: 605-608 exclusive. For instance, migraine can precipitate 11. Jacome DE, Yanez GF. Transient global amnesia seizures, seizures can cause post-ictal TGA and and left frontal hemorrhage. Postgrad Med (1988) J history of migraine may facilitate the eventual 64: 137-139 appearance of TGA in a given subject. Given the 12. Litch JA, Bishop RA. Transient global amnesia at potential occurrence of migraine without headache as high altitude. N Engl J Med (1999) 340: 1444 a persistent aura, in particular in older patients 13. Pascual J, Iglesias F, Oterino A, ("migraine with late accompaniments"), and the known Vazquez-Barquero A, Berciano J Cough, exertional, association between CSD, migraine and ischemia, as and sexual headaches: an analysis of 72 benign and well as between cough and headache, it is legitimate symptomatic cases. Neurology (1996) 46: 1520-1524 to speculate that abrupt and sustained changes in 14. Lane RJM, Davies PTG Modified Valsava test cerebral venous return during prolonged coughing in differentiates primary from secondary cough headache. these two patients, resulted in unilateral hippocampus J Headache Pain (2013) 14:31 ischemia and TGA, as an isolated persistent cognitive 15. Jacome DE, Stamm M Malignant cough headache. migraine aura (24). Headache (2004) 44:259-261 16. Sevgi EB, Erdener SE, Demirici M, Topcuoglu MA, Conclusion Dalkara T. Paradoxical air microembolism induces cerebral bioelectrical abnormalities and occasionally headache in patent foramen ovale patients with It is suggested that selective transient ischemia of the migraine. J Am Heart assoc (2012) 1 (6):e001735 hippocampus during coughing crisis may E-Pub Dec 19 precipitate TGA in exceptional patients, as a form of 17. Jacome DE La toux diabolique: neurogenic tussive cough-induced persistent cognitive migraine aura crisis. Post Grad Med J (1985) 61: 515-516 without stroke. 18. Spring PJ, Kok C, Nicholson GA, Ing AJ, Spies JM, Bassett ML, Cameron J, Kerlin P, Bowler S, Tuck R, References Pollard JD. Autosomal dominant hereditary sensory neuropathy with chronic cough and gastro-esophageal reflux: clinical features in two families linked to 1. Fisher CM, Adams RD. Transient Global Amnesia. chromosome 3p22-p24. Brain (2005) 128: 2797-2810 Acta Neurol Scand (1964) 40 (suppl 9) 7-83 19. Niimi A, Kihara Y, Sumita Y, Okano Y, Tambara K, 2. Jacome DE. Transient Global Amnesia: Clinical and Fujita M. Cough reflex by ventricular premature EEG considerations. Am J EEG Technol (1990) contractions. Int Heart J (2005) 46: 923-926 30:195-209 20. Nakada T, Kwee IL, Fujii Y, Knight RT High-field, 3. Cantor FK. Transient global amnesia and temporal T2 reversal MRI of the hippocampus in transient global lobe seizures. Neurology (1971) 21: 430-431 amnesia. Neurology (2005) 64:1170-1174 4. Crowell GF, Stump DA, Biller J, McHenry LC, Toole 21. Chung CP, Hsu HY, Chao AC, Chang FC, Sheng JF. The transient global amnesia-migraine connection. WY, Hu HH. Detection of intracranial venous reflux in Arch Neurol (1984) 41:75-79 patients of transient global amnesia. Neurology (2006) 5. Jacome DE. Cardiac testing in transient global 66: 1873-1877 amnesia (TGA). Neurology (1988) 38: (suppl 1) 413 22. Sedlaczek O, Hirsch JG, Grips E, Peters CNA, 6. Pietrini V, Terzano MG, D’Andrea G, Parrino L, Gass A, Whorle J, Hennerici M. Detection of delayed Cananzi AR, Ferro-Milone F. Acute confusional focal MR changes in the lateral hippocampus in migraine: clinical and electroencephalographic aspects. transient global amnesia. Neurology (2004) 62: Cephalagia (1987) 7: 29-37 2165-2170 7. Jacome DE. EEG features in transient global 23. Olesen J, Jorgensen MB. Leao’s spreading

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depression in the hippocampus explains transient global amnesia. Acta Neurol Scand (1986) 73: 219-220 24. Charles AC, Baca SM. Cortical spreading depression and migraine. Nat.Rev.Neurol (2013) advanced on line publication, 17 of september, 1-7

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