ISSN 0017-8748 0017-8748 ISSN doi: 10.1111/head.12595 10.1111/head.12595 doi: Published Inc. Published by by Wiley Wiley Periodicals, Periodicals, Inc.
Headache Headache C 2015 American Headache Society V © 2015 American Headache Society
Brief Communication Familial Hemiplegic Migraine and Recurrent Episodes of Psychosis: A Case Report Sonja LaBianca; Rigmor Jensen, MD, PhD; Arn M.J.M. van den Maagdenberg, MD, PhD; Lone Baandrup, MD, PhD; Lars Bendtsen, MD, PhD
Familial hemiplegic migraine (FHM) is a rare autosomal dominant form of migraine with motor aura. We present a case report of a father and son with very similar attacks of hemiplegic migraine and recurrent episodes of accompanying psychoses. Previously, such episodes led to hospitalization and extended clinical examinations, which further worsened the psychoses. Since the episodes were recognized as related to the hemiplegic migraine, a treatment strategy combining sleep and sedation was initiated and progression onto psychosis was almost completely avoided in both father and son. Genetic analyses found no causal gene mutation in the three known FHM genes, suggesting that the phenotype is caused by a yet unidentified mutation. Key words: delirium, familial hemiplegic migraine, psychosis
(Headache 2015;••:••-••) 2015;55:1004-1007)
Familial hemiplegic migraine (FHM) is a rare form of migraine with aura (MA) that involves motor aura. A diagnosis of FHM requires at least 2 attacks presenting with reversible motor weakness and at least 1 other transient neurological symptom.1 Motor symptoms usually persist for less than 72 hours but may last for days. Similar episodes should be present in at least 1 first-degree or second-degree relative.1
From the Danish Headache Center, Department of Neurology Glostrup, Copenhagen University Hospital, Glostrup, Denmark (S. LaBianca, R. Jensen, and L Bendtsen); Departments of Human Genetics & Neurology, Leiden University Medical Center, Leiden, The Netherlands (A.M.J.M. van den Maagdenberg); Center for Neuropsychiatric Schizophrenia Research, Mental Health Center Glostrup, Copenhagen University Hospital, Glostrup, Denmark (L. Baandrup). Address all correspondence to L. Bendtsen, Danish Headache Center, Department of Neurology, Glostrup Hospital, Faculty of Health Sciences, University of Copenhagen, Glostrup, DK 2600, Denmark.
FHM is dominantly inherited and 3 FHM genes (CACNA1A, ATP1A2, and SCN1A) have been identified, all encoding proteins involved in ion transportation.2 Not all families present with a mutation in one of these genes, suggesting that there are additional FHM genes;3 indeed, the PRRT2 gene was recently put forward as a possible additional FHM gene,4 but present genetic evidence for this claim has recently been challenged.5 The clinical presentation of FHM attacks may vary among relatives with the same mutation and may also include a variety of neurological symptoms besides motor weakness.3 Rarely, disturbance of consciousness, agitation, seizures, fever, or cerebrospinal fluid (CSF) pleocytosis occurs.3,6 Here we present a case report of a father and son with very similar attacks of hemiplegic migraine and recurrent episodes of severe and long-lasting confusion and psychosis. Conflict of Interest: None.
Accepted for publication April 3, 2015.
Financial Support: None.
1004 1
Headache 2
CASE REPORT The proband is 70 years old and right handed. He is overweight, smokes daily, and suffers from diabetes and hypertension. Since his late teens, he has had attacks of migraine always preceded by aura. Frequency has varied from 6 per month till a few per year; attacks are often triggered by stress. Typically an attack presents with 15-20 minutes of visual disturbances, described as difficulties of reading a text, followed by sensory disturbances of pins and needles spreading from fingers to arm, shoulder, and face.Visual disturbances can be unilateral or bilateral, whereas sensory symptoms always locate to one side only and persist for 30-60 minutes occasionally including the ipsilateral lower extremity. Approximately 25% of the attacks proceed onto motor weakness of the affected side, which might last for days. In approximately half of the episodes with focus localized to the left hemisphere, the patient becomes dysphasic for hours or even days. The aura is always followed by a unilateral migraine headache contralateral to aura symptoms, lasting between several hours and 3 days. From 1980 to 2013, the proband has experienced 9 long-lasting episodes of severe confusion and psychosis, always preceded by an attack of hemiplegic migraine. According to his wife, symptoms of confusion and psychosis develop during migraine headache or with a latent period of hours or up to 2 days. He describes hallucinations with remarkable detail, eg, seeing chainsaws in the ceiling or smoke coming out of his legs, the presence of imaginary persons in the room, and sometimes hearing commenting voices. He has been hospitalized in neurological departments for a total of 4 times when such episodes occurred. Here he was observed as being confused and disorganized, often aggressive and uneasy but at times in a stage of stupor, as well as dysphasic and hemiplegic. The sleep pattern was affected with short sleep cycles and frequent awakenings. An episode could last from few days till a week. In 1997, he was discharged from hospital before the psychotic episode was over. Arriving at home, he jumped out of a window from the second floor and fractured a lumbar vertebra. In his hallucinations, he had thought that he was sitting on the back of
1005 a truck that was driving off a cliff, and therefore had to jump off. In 2008, he was referred to the Danish Headache Centre (DHC), a tertiary headache center.7 Until then, it was not recognized that episodes of confusion and psychosis in this patient were related to the hemiplegic migraine. Episodes had been suspected as central nervous system (CNS) infection, stroke, or epilepsy, taking him through repetitive extensive workups including repetitive ictal and interictal electroencephalographs (EEGs). These were normal except for one showing slightly abnormal 1-3 Hz activities frontal on left side considered a nonsignificant finding. Otherwise no abnormal findings were identified, including repetitive normal computerized tomography of the brain (CTC), magnetic resonance imaging (MRI), single-photon emission computerized tomography (SPECT), CSF examinations, and blood tests. These interventions seemed to significantly worsen and prolong his symptoms of confusion and psychosis. When admitted to DHC, he used sodium valproate 500 mg daily as preventive medication for MA. Due to side effects and lack of efficacy, it was discontinued. His medications were adjusted to diazepam 5 mg in case of MA supplemented with levomepromazine 12.5-25 mg if needed. Levomepromazine was used as a sedative, not as an antipsychotic, and was chosen because the treating neurologist (LBe) has extensive experience with this drug from treating patients with medication-overuse headache during detoxification.This therapeutic strategy combined with sleep and rest has since had good effect on preventing the progression of symptoms. The proband’s father had migraines, but it was uncertain whether he had aura, hemiparesis, confusion, or psychotic symptoms. Interestingly, the proband’s son has had very similar attacks of hemiplegic migraine. He is 44 years old, right handed, overweight, and a smoker. Onset of MA was in his late teens. The frequency has always varied a lot from few mild attacks per year till intense clusters of several severe attacks per week, often triggered by stress related to his job. In his case, there have been 4 episodes of long lasting severe confusion and psychosis following an attack of hemiplegic migraine. He has
1006 Headache been hospitalized several times and was once transferred to the psychiatric department for 3 days and treated with forced medication and fixation due to severe aggressions and uneasiness in his psychotic state. During this episode, the nocturnal sleep was disrupted with frequent awakenings; he had a fever and rise of blood leukocytes, but no rise of erythrocyte sedimentation rate or other biochemical parameters. CTC, MRI, EEG, and CSF examinations during the other episodes showed no abnormal findings. He has also been a patient at the DHC and his migraine attacks are now well controlled with diclofenac, supplemented by diazepam in case of confusion and psychotic symptoms. Stress reduction has been beneficial in reducing the frequency and intensity of attacks. Therefore, he has no need of preventive medication. Genetic analysis performed on blood samples from father and son revealed no causal mutation in the 3 previous identified FHM genes as was assessed by sequencing the coding exons and the directly flanking intronic sequences.
DISCUSSION We present a case report of a father and son with very similar phenotypes. To date, there have been few similar case reports published.8-12 It could be considered whether such cases truly are rare or more likely misdiagnosed and underreported. To our knowledge, this is the first case in which no mutation was identified in a family with FHM and accompanying episodes of psychosis. A yet unidentified genetic mutation might be responsible for the inherited phenotype of combined hemiplegic migraine and recurrent episodes of confusion and psychotic symptoms in this small family. Confusion and psychotic symptoms following the hemiplegic migraine attack could be considered as either a prolonged aura or a state of delirium. This is a challenging diagnostic differentiation, considering that an understanding of the neuro-pathological mechanisms underlying both conditions still remains to be fully understood. In this case report, a diagnostic differentiation must relay on clinical data, since we lack specific biological markers for a diagnosis of both conditions. A state of delirium13 would be in agree-
July/August 2015 3 ment with the acute onset of symptoms, altered consciousness, disorganization, changes of psychomotor behavior, and disrupted sleep-wake cycle as well as psychotic symptoms described in this case. The organic basis for development of delirium could be the brain changes associated with the preceding hemiplegic migraine. Decreased arterial blood flow14 and cortical spreading depression can induce universal energy deprivation and hypoxia of the brain and might also play a role in decreased cholinergic transmission.15 Currently, the best-documented treatment regimen of delirious states is haloperidol, which is effective in both prevention and for decreasing duration and severity.16 Anticholinergic drugs are believed to aggravate delirium. The efficacy of levomepromazine administered in our case reports probably reflects the successful rapid induction of sleep and subsequent resolution of the condition. Alternatively, if symptoms present a phase of prolonged aura, one could consider that mechanisms of cortical spreading depression3 reach anatomical structures involved in consciousness (formatio reticularis) and psychosis (subcortical/ limbic structures). Previous case reports have presented other atypical aura symptoms in patients with FHM.3,6,10 Furthermore, it is well documented that impaired consciousness and long duration of aura symptoms in severe hemiplegic migraine attacks might last several days till months until full recovery is achieved.3 Concerning implications for diagnosis and treatment of similar cases, we recommend that the patient is given rest and that symptoms are evaluated as either an aura phenomenon or a delirious state and treated accordingly. Obviously, this requires thorough workup initially to exclude other causes of the symptoms. Further detailed genetic analysis may provide valuable insight in the underlying mechanisms of the fascinating migraine/psychosis spectrum. Acknowledgments: We thank the proband and his son for giving consent to this presentation.
STATEMENT OF AUTHORSHIP Category 1 (a) Conception and Design Sonja LaBianca, Lars Bendtsen
Headache 4 (b) Acquisition of Data Sonja LaBianca, Lars Bendtsen (c) Analysis and Interpretation of Data Sonja LaBianca, Rigmor Jensen, Arn M.J.M van den Maagdenberg, Lone Baandrup, Lars Bendtsen Category 2 (a) Drafting the Manuscript Sonja LaBianca (b) Revising It for Intellectual Content Sonja LaBianca, Rigmor Jensen, Arn M.J.M van den Maagdenberg, Lone Baandrup, Lars Bendtsen Category 3 (a) Final Approval of the Completed Manuscript Sonja LaBianca, Rigmor Jensen, Arn M.J.M van den Maagdenberg, Lone Baandrup, Lars Bendtsen
1007
7.
8.
9.
10.
11.
REFERENCES 1. Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013;33:629-808. 2. de Vries B, Frants RR, Ferrari MD, van den Maagdenberg AM. Molecular genetics of migraine. Hum Genet. 2009;126:115-132. 3. Russell MB, Ducros A. Sporadic and familial hemiplegic migraine: Pathophysiological mechanisms, clinical characteristics, diagnosis, and management. Lancet Neurol. 2011;10:457-470. 4. Riant F, Roze E, Barbance C, et al. PRRT2 mutations cause hemiplegic migraine. Neurology. 2012;79:2122-2124. 5. Pelzer N, de Vries B, Kamphorst JT, et al. PRRT2 and hemiplegic migraine: A complex association. Neurology. 2014;83:288-290. 6. Ducros A, Denier C, Joutel A, et al. The clinical spectrum of familial hemiplegic migraine associated
12.
13.
14.
15. 16.
with mutations in a neuronal calcium channel. N Engl J Med. 2001;345:17-24. Jensen R, Zeeberg P, Dehlendorff C, Olesen J. Predictors of outcome of the treatment programme in a multidisciplinary headache centre. Cephalalgia. 2010;30:1214-1224. Moreira T, Menetrey A, Carota A. Neurological picture. Cortical oedema: A link between delusional misidentification syndromes and hemiplegic migraine. J Neurol Neurosurg Psychiatry. 2010;81:52-53. Barros J, Mendes A, Matos I, Pereira-Monteiro J. Psychotic aura symptoms in familial hemiplegic migraine type 2 (ATP1A2). J Headache Pain. 2012;13:581-585. Spranger M, Spranger S, Schwab S, Benninger C, Dichgans M. Familial hemiplegic migraine with cerebellar ataxia and paroxysmal psychosis. Eur Neurol. 1999;41:150-152. Fuller GN, Marshall A, Flint J, Lewis S, Wise RJ. Migraine madness: Recurrent psychosis after migraine. J Neurol Neurosurg Psychiatry. 1993;56:416-418. Feely MP, O’Hare J, Veale D, Callaghan N. Episodes of acute confusion or psychosis in familial hemiplegic migraine. Acta Neurol Scand. 1982;65:369-375. World Health Organization. The ICD-10 classification of mental and behavioural disorders. Int Classif. 1992;10:1-267. Olesen J, Friberg L, Olsen TS, et al. Timing and topography of cerebral blood flow, aura, and headache during migraine attacks. Ann Neurol. 1990;28:791-798. Burns A, Gallagley A, Byrne J. Delirium. J Neurol Neurosurg Psychiatry. 2004;75:362-367. Friedman JI, Soleimani L, McGonigle DP, Egol C, Silverstein JH. Pharmacological treatments of nonsubstance-withdrawal delirium: A systematic review of prospective trials. Am J Psychiatry. 2014;171:151159.
Headache Headache C 2015 American Headache Society V © 2015 American Headache Society
Brief Communication Familial Hemiplegic Migraine and Recurrent Episodes of Psychosis: A Case Report Sonja LaBianca; Rigmor Jensen, MD, PhD; Arn M.J.M. van den Maagdenberg, MD, PhD; Lone Baandrup, MD, PhD; Lars Bendtsen, MD, PhD
Familial hemiplegic migraine (FHM) is a rare autosomal dominant form of migraine with motor aura. We present a case report of a father and son with very similar attacks of hemiplegic migraine and recurrent episodes of accompanying psychoses. Previously, such episodes led to hospitalization and extended clinical examinations, which further worsened the psychoses. Since the episodes were recognized as related to the hemiplegic migraine, a treatment strategy combining sleep and sedation was initiated and progression onto psychosis was almost completely avoided in both father and son. Genetic analyses found no causal gene mutation in the three known FHM genes, suggesting that the phenotype is caused by a yet unidentified mutation. Key words: delirium, familial hemiplegic migraine, psychosis
(Headache 2015;••:••-••) 2015;55:1004-1007)
Familial hemiplegic migraine (FHM) is a rare form of migraine with aura (MA) that involves motor aura. A diagnosis of FHM requires at least 2 attacks presenting with reversible motor weakness and at least 1 other transient neurological symptom.1 Motor symptoms usually persist for less than 72 hours but may last for days. Similar episodes should be present in at least 1 first-degree or second-degree relative.1
From the Danish Headache Center, Department of Neurology Glostrup, Copenhagen University Hospital, Glostrup, Denmark (S. LaBianca, R. Jensen, and L Bendtsen); Departments of Human Genetics & Neurology, Leiden University Medical Center, Leiden, The Netherlands (A.M.J.M. van den Maagdenberg); Center for Neuropsychiatric Schizophrenia Research, Mental Health Center Glostrup, Copenhagen University Hospital, Glostrup, Denmark (L. Baandrup). Address all correspondence to L. Bendtsen, Danish Headache Center, Department of Neurology, Glostrup Hospital, Faculty of Health Sciences, University of Copenhagen, Glostrup, DK 2600, Denmark.
FHM is dominantly inherited and 3 FHM genes (CACNA1A, ATP1A2, and SCN1A) have been identified, all encoding proteins involved in ion transportation.2 Not all families present with a mutation in one of these genes, suggesting that there are additional FHM genes;3 indeed, the PRRT2 gene was recently put forward as a possible additional FHM gene,4 but present genetic evidence for this claim has recently been challenged.5 The clinical presentation of FHM attacks may vary among relatives with the same mutation and may also include a variety of neurological symptoms besides motor weakness.3 Rarely, disturbance of consciousness, agitation, seizures, fever, or cerebrospinal fluid (CSF) pleocytosis occurs.3,6 Here we present a case report of a father and son with very similar attacks of hemiplegic migraine and recurrent episodes of severe and long-lasting confusion and psychosis. Conflict of Interest: None.
Accepted for publication April 3, 2015.
Financial Support: None.
1004 1
Headache 2
CASE REPORT The proband is 70 years old and right handed. He is overweight, smokes daily, and suffers from diabetes and hypertension. Since his late teens, he has had attacks of migraine always preceded by aura. Frequency has varied from 6 per month till a few per year; attacks are often triggered by stress. Typically an attack presents with 15-20 minutes of visual disturbances, described as difficulties of reading a text, followed by sensory disturbances of pins and needles spreading from fingers to arm, shoulder, and face.Visual disturbances can be unilateral or bilateral, whereas sensory symptoms always locate to one side only and persist for 30-60 minutes occasionally including the ipsilateral lower extremity. Approximately 25% of the attacks proceed onto motor weakness of the affected side, which might last for days. In approximately half of the episodes with focus localized to the left hemisphere, the patient becomes dysphasic for hours or even days. The aura is always followed by a unilateral migraine headache contralateral to aura symptoms, lasting between several hours and 3 days. From 1980 to 2013, the proband has experienced 9 long-lasting episodes of severe confusion and psychosis, always preceded by an attack of hemiplegic migraine. According to his wife, symptoms of confusion and psychosis develop during migraine headache or with a latent period of hours or up to 2 days. He describes hallucinations with remarkable detail, eg, seeing chainsaws in the ceiling or smoke coming out of his legs, the presence of imaginary persons in the room, and sometimes hearing commenting voices. He has been hospitalized in neurological departments for a total of 4 times when such episodes occurred. Here he was observed as being confused and disorganized, often aggressive and uneasy but at times in a stage of stupor, as well as dysphasic and hemiplegic. The sleep pattern was affected with short sleep cycles and frequent awakenings. An episode could last from few days till a week. In 1997, he was discharged from hospital before the psychotic episode was over. Arriving at home, he jumped out of a window from the second floor and fractured a lumbar vertebra. In his hallucinations, he had thought that he was sitting on the back of
1005 a truck that was driving off a cliff, and therefore had to jump off. In 2008, he was referred to the Danish Headache Centre (DHC), a tertiary headache center.7 Until then, it was not recognized that episodes of confusion and psychosis in this patient were related to the hemiplegic migraine. Episodes had been suspected as central nervous system (CNS) infection, stroke, or epilepsy, taking him through repetitive extensive workups including repetitive ictal and interictal electroencephalographs (EEGs). These were normal except for one showing slightly abnormal 1-3 Hz activities frontal on left side considered a nonsignificant finding. Otherwise no abnormal findings were identified, including repetitive normal computerized tomography of the brain (CTC), magnetic resonance imaging (MRI), single-photon emission computerized tomography (SPECT), CSF examinations, and blood tests. These interventions seemed to significantly worsen and prolong his symptoms of confusion and psychosis. When admitted to DHC, he used sodium valproate 500 mg daily as preventive medication for MA. Due to side effects and lack of efficacy, it was discontinued. His medications were adjusted to diazepam 5 mg in case of MA supplemented with levomepromazine 12.5-25 mg if needed. Levomepromazine was used as a sedative, not as an antipsychotic, and was chosen because the treating neurologist (LBe) has extensive experience with this drug from treating patients with medication-overuse headache during detoxification.This therapeutic strategy combined with sleep and rest has since had good effect on preventing the progression of symptoms. The proband’s father had migraines, but it was uncertain whether he had aura, hemiparesis, confusion, or psychotic symptoms. Interestingly, the proband’s son has had very similar attacks of hemiplegic migraine. He is 44 years old, right handed, overweight, and a smoker. Onset of MA was in his late teens. The frequency has always varied a lot from few mild attacks per year till intense clusters of several severe attacks per week, often triggered by stress related to his job. In his case, there have been 4 episodes of long lasting severe confusion and psychosis following an attack of hemiplegic migraine. He has
1006 Headache been hospitalized several times and was once transferred to the psychiatric department for 3 days and treated with forced medication and fixation due to severe aggressions and uneasiness in his psychotic state. During this episode, the nocturnal sleep was disrupted with frequent awakenings; he had a fever and rise of blood leukocytes, but no rise of erythrocyte sedimentation rate or other biochemical parameters. CTC, MRI, EEG, and CSF examinations during the other episodes showed no abnormal findings. He has also been a patient at the DHC and his migraine attacks are now well controlled with diclofenac, supplemented by diazepam in case of confusion and psychotic symptoms. Stress reduction has been beneficial in reducing the frequency and intensity of attacks. Therefore, he has no need of preventive medication. Genetic analysis performed on blood samples from father and son revealed no causal mutation in the 3 previous identified FHM genes as was assessed by sequencing the coding exons and the directly flanking intronic sequences.
DISCUSSION We present a case report of a father and son with very similar phenotypes. To date, there have been few similar case reports published.8-12 It could be considered whether such cases truly are rare or more likely misdiagnosed and underreported. To our knowledge, this is the first case in which no mutation was identified in a family with FHM and accompanying episodes of psychosis. A yet unidentified genetic mutation might be responsible for the inherited phenotype of combined hemiplegic migraine and recurrent episodes of confusion and psychotic symptoms in this small family. Confusion and psychotic symptoms following the hemiplegic migraine attack could be considered as either a prolonged aura or a state of delirium. This is a challenging diagnostic differentiation, considering that an understanding of the neuro-pathological mechanisms underlying both conditions still remains to be fully understood. In this case report, a diagnostic differentiation must relay on clinical data, since we lack specific biological markers for a diagnosis of both conditions. A state of delirium13 would be in agree-
July/August 2015 3 ment with the acute onset of symptoms, altered consciousness, disorganization, changes of psychomotor behavior, and disrupted sleep-wake cycle as well as psychotic symptoms described in this case. The organic basis for development of delirium could be the brain changes associated with the preceding hemiplegic migraine. Decreased arterial blood flow14 and cortical spreading depression can induce universal energy deprivation and hypoxia of the brain and might also play a role in decreased cholinergic transmission.15 Currently, the best-documented treatment regimen of delirious states is haloperidol, which is effective in both prevention and for decreasing duration and severity.16 Anticholinergic drugs are believed to aggravate delirium. The efficacy of levomepromazine administered in our case reports probably reflects the successful rapid induction of sleep and subsequent resolution of the condition. Alternatively, if symptoms present a phase of prolonged aura, one could consider that mechanisms of cortical spreading depression3 reach anatomical structures involved in consciousness (formatio reticularis) and psychosis (subcortical/ limbic structures). Previous case reports have presented other atypical aura symptoms in patients with FHM.3,6,10 Furthermore, it is well documented that impaired consciousness and long duration of aura symptoms in severe hemiplegic migraine attacks might last several days till months until full recovery is achieved.3 Concerning implications for diagnosis and treatment of similar cases, we recommend that the patient is given rest and that symptoms are evaluated as either an aura phenomenon or a delirious state and treated accordingly. Obviously, this requires thorough workup initially to exclude other causes of the symptoms. Further detailed genetic analysis may provide valuable insight in the underlying mechanisms of the fascinating migraine/psychosis spectrum. Acknowledgments: We thank the proband and his son for giving consent to this presentation.
STATEMENT OF AUTHORSHIP Category 1 (a) Conception and Design Sonja LaBianca, Lars Bendtsen
Headache 4 (b) Acquisition of Data Sonja LaBianca, Lars Bendtsen (c) Analysis and Interpretation of Data Sonja LaBianca, Rigmor Jensen, Arn M.J.M van den Maagdenberg, Lone Baandrup, Lars Bendtsen Category 2 (a) Drafting the Manuscript Sonja LaBianca (b) Revising It for Intellectual Content Sonja LaBianca, Rigmor Jensen, Arn M.J.M van den Maagdenberg, Lone Baandrup, Lars Bendtsen Category 3 (a) Final Approval of the Completed Manuscript Sonja LaBianca, Rigmor Jensen, Arn M.J.M van den Maagdenberg, Lone Baandrup, Lars Bendtsen
1007
7.
8.
9.
10.
11.
REFERENCES 1. Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013;33:629-808. 2. de Vries B, Frants RR, Ferrari MD, van den Maagdenberg AM. Molecular genetics of migraine. Hum Genet. 2009;126:115-132. 3. Russell MB, Ducros A. Sporadic and familial hemiplegic migraine: Pathophysiological mechanisms, clinical characteristics, diagnosis, and management. Lancet Neurol. 2011;10:457-470. 4. Riant F, Roze E, Barbance C, et al. PRRT2 mutations cause hemiplegic migraine. Neurology. 2012;79:2122-2124. 5. Pelzer N, de Vries B, Kamphorst JT, et al. PRRT2 and hemiplegic migraine: A complex association. Neurology. 2014;83:288-290. 6. Ducros A, Denier C, Joutel A, et al. The clinical spectrum of familial hemiplegic migraine associated
12.
13.
14.
15. 16.
with mutations in a neuronal calcium channel. N Engl J Med. 2001;345:17-24. Jensen R, Zeeberg P, Dehlendorff C, Olesen J. Predictors of outcome of the treatment programme in a multidisciplinary headache centre. Cephalalgia. 2010;30:1214-1224. Moreira T, Menetrey A, Carota A. Neurological picture. Cortical oedema: A link between delusional misidentification syndromes and hemiplegic migraine. J Neurol Neurosurg Psychiatry. 2010;81:52-53. Barros J, Mendes A, Matos I, Pereira-Monteiro J. Psychotic aura symptoms in familial hemiplegic migraine type 2 (ATP1A2). J Headache Pain. 2012;13:581-585. Spranger M, Spranger S, Schwab S, Benninger C, Dichgans M. Familial hemiplegic migraine with cerebellar ataxia and paroxysmal psychosis. Eur Neurol. 1999;41:150-152. Fuller GN, Marshall A, Flint J, Lewis S, Wise RJ. Migraine madness: Recurrent psychosis after migraine. J Neurol Neurosurg Psychiatry. 1993;56:416-418. Feely MP, O’Hare J, Veale D, Callaghan N. Episodes of acute confusion or psychosis in familial hemiplegic migraine. Acta Neurol Scand. 1982;65:369-375. World Health Organization. The ICD-10 classification of mental and behavioural disorders. Int Classif. 1992;10:1-267. Olesen J, Friberg L, Olsen TS, et al. Timing and topography of cerebral blood flow, aura, and headache during migraine attacks. Ann Neurol. 1990;28:791-798. Burns A, Gallagley A, Byrne J. Delirium. J Neurol Neurosurg Psychiatry. 2004;75:362-367. Friedman JI, Soleimani L, McGonigle DP, Egol C, Silverstein JH. Pharmacological treatments of nonsubstance-withdrawal delirium: A systematic review of prospective trials. Am J Psychiatry. 2014;171:151159.
