Abstract
Background: Acute confusional migraine (ACM) is considered a rare migraine variant primarily seen in children and adolescents.
Patients and Methods: We present a series of eight adults and two adolescents suffering from migraine attacks associated with transient confusional states.
Results: Eight patients reported two or more such attacks. One of them reported mild head trauma in the past. One patient reported mild head trauma as a possible trigger. Further investigations were unremarkable in all patients and did not suggest underlying structural abnormalities, epilepsy or cerebrovascular disease. In none of these patients did we find another cause to explain the observed phenomenon.
Conclusions: Based on this series of patients, we suggest expanding the concept of confusional migraine from the paediatric population to adults. The temporal course of the confusion as well as the association with visual and other aura symptoms suggest cortical spreading depression as the underlying pathophysiology.
Introduction
Demographics and clinical features of the published cases of acute confusional migraine
Adapted from Neinstein et al. (3).
NR, not reported.
All patients had CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy).
Cases
Case 1
A 16-year-old adolescent had a slight frontal head pain towards the end of a soccer game. On the way home, he vomited repeatedly. At home, he experienced left-sided numbness slowly spreading from the lips to the cheek. He was seen by his general practitioner (GP) who diagnosed a migraine attack. When he became disorientated in time and space, he was sent to our emergency department. He had a history of episodic migraine since childhood occurring up to four times a year, with a similar confusional episode associated with a migraine attack one year ago. His mother also suffered from headaches. At the emergency department, the patient was not continuously orientated towards time and space; otherwise, the neurological examination was normal. The numbness had completely resolved before admission. He fully regained orientation within 2 h. He had normal blood tests and a normal computed tomography (CT) scan. An magnetic resonance imaging (MRI) scan of the brain was normal.
Case 2
A 36-year-old woman presented to our out-patient headache clinic with a history of migraine with and without visual aura beginning at the age of 11 years. On average, she had two attacks per month. In the last year, she had experienced several episodes of transient disorientation with impairment of episodic memory and spatial orientation following her migraine attacks which lasted for several hours. For instance, she did not remember whether her best friend was married or not and, after another attack, she had difficulties in orientating in her familiar environment. She was treated with citalopram and clomipramine because of social phobia with panic attacks and depressive episodes. Otherwise, she was healthy. The family history was negative for headaches. Neurological examination did not reveal any pathology except for amblyopy of the left eye since childhood. A neuropsychological examination showed discrete verbal and spatial short-term memory deficiency which was attributed to perinatal damage. An MRI scan of the brain was normal. She had previously been investigated for epilepsy, but all EEGs were normal.
Case 3
A 22-year-old woman presented to our out-patient headache clinic with a history of migraine with and without aura for 7 years. She had migraine attacks with preceding visual and/or sensory aura on 4–5 days per month. Occasionally, she had isolated auras. About 6 months prior to referral, she had a typical migraine with visual aura followed by a state of confusion lasting for 2–3 h. She had problems in finding words. Trying to telephone her mother, she was unable to recall the pin code of her mobile phone. She mistook her alarm clock for the telephone receiver. The confusion resolved completely during sleep; the headache lasted for another 3 h. Otherwise, she was healthy. Her father suffered from migraine with and without aura. The neurological examination was normal, as well as a previous MRI of the brain. An interictal EEG 3 months after the confusional state showed no pathology. The patient refused neuropsychological testing and cancelled her follow-up visit, as she had only suffered from one isolated visual aura in the month after her first visit. No further confusional episode had occurred in that period, as reported by the patient on the telephone.
Case 4
A 16-year-old, right-handed girl suddenly had difficulties reading during a French lesson at school due to a scotoma in her right visual field. Following the visual problems, she was unable to write. While leaving the classroom, she was afraid of her classmates, whom she did not recognise anymore. She even forgot her own name. Subsequently, she developed a severe throbbing unilateral headache. She had a history of recurrent unilateral throbbing headaches for 1 year which were triggered by stressful events at school. Otherwise, she was healthy and did not take any medication. Her mother suffered from migraine with visual aura. The neurological and a thorough neuropsychological examination were normal. An MRI scan of the brain, an ictal EEG and routine blood screening were also unremarkable.
Case 5
A 30-year-old man with a history of severe episodic unilateral headache with nausea, which occurred about once per week, consulted his GP because of a common cold lasting longer than 3 weeks. During arterial blood taking from the finger tip, he felt a slight dizziness. After 10–15 min, he was seeing the GP for discussion of the blood test (C-reactive protein level) that was normal. During the consultation, the GP noticed slurred speech with some paraphasia. Then, the patient appeared agitated and confused with signs of apraxia: he was helpless, unable to put on his coat when leaving. After 30 min, he developed a severe throbbing pain on the right forehead, associated with nausea and vomiting. When admitted to our emergency department 2 h later, the pain had already improved and the mental status was normal. Neurological examination was unremarkable. As the patient was free of any complaints, he refused further examinations such as an MRI scan of the brain and an EEG. He did not have similar episodes in the next 3 months.
Case 6
A 41-year-old man was admitted to the emergency ward because of an acute confusional state with temporal and spatial disorientation. He had been standing in his kitchen, fully disorientated, speaking incoherently and not recognizing his neighbours. A CT scan of the brain was normal. He suffered from moderate frontal headache with nausea. The next day, he had severe holocranial headache associated with unilateral visual disturbances and nausea. He was fully orientated at that time. He was followed up in our out-patient headache clinic 7 months later. No further confusional episode had occurred in the mean time. The neurological examination was normal. An EEG did not reveal any abnormalities. The patient had complete amnesia for the confusional episode described above.
He had a history of migraine with visual and sensory aura since childhood. He had 4–5 headache days per month and treated attacks with naratriptan. Confusional episodes associated with migraine had occurred several times before. The patient always had complete amnesia for these episodes lasting several hours. He also had a history of major depression and anxiety disorder and was treated with venlafaxin 37.5 mg/day. The patient was scheduled for cranial MRI but was lost for follow-up.
Case 7
For several years, this 41-year-old man had moderate headaches preceded by visual aura in about half of the cases. The headaches changed approximately 6 weeks after he was attacked by a group of adolescents and suffered from a polytrauma with head trauma, luxation of the shoulder, rib fractures, and contusions of the cervical spine. Since then, headaches following visual aura became more severe and were accompanied by nausea, sometimes emesis, photo- and phonophobia. During the headache phase, he was in a state of confusion for about 60–90 min, e.g. he did not recognise his physiotherapist on the telephone or he forgot about appointments. These attacks occurred up to three times per week over a period of 4 months. Thereafter, he went back to the previous, less severe migraines. He was otherwise healthy. An MRI scan of the brain was normal.
Case 8
A 62-year-old man had suffered from migraine since the age of 9 years, with mostly one to two attacks per month. He had severe unilateral or holocranial headaches, lasting for about 5 h associated with photophobia, phonophobia, and nausea. In the last 10 years, he suffered from typical visual auras once or twice per year, occasionally followed by the headaches described above. Sometimes, the patient suffered from numbness of the tongue during headache attacks. He also reported of three confusional episodes associated with migraine attacks. The first episode occurred several years ago while the patient was working in his office. He had difficulty realising what was going on. Thinking and speech were slowed with distorted words. Later, he could not remember names of his colleagues. He suffered from another two similar episodes. All episodes were associated with migraines and fully reversible after about one hour. The patient’s father also suffered from migraine. Neurological examination was normal. An MRI of the brain 4 years ago showed frontal micro-infarcts. A recent EEG showed discrete intermittent right temporal slowing.
Case 9
A 19-year-old man suffered from severe migraine attacks with or without aura since the age of 6 years. As a child, he had attacks only occasionally. For the last 2 years, he had 2–4 attacks per month. The severe headache was unilateral, mostly frontoparietally located with a duration of up to 2 days without treatment. It was accompanied by photophobia, phonophobia and nausea. In most attacks, naratriptan relieved the headache after 2–4 h. Aura symptoms were always associated with migraine headache and included most often visual symptoms followed by aphasia.
At the age of 19 years, the patient was referred to our hospital since he developed unusual aura symptoms and headache after playing soccer. At the beginning, he experienced a moderate right hemispheric headache which became severe after an hour. He developed left-sided central facial palsy which lasted for about 30 min. After that, he was not responsive for few minutes and then presented with dysphasia with strong reduction in spontaneous speech, use of simple and short words, incomplete sentences and incorrect grammar. He understood simple sentences only. His actions appeared apractic. He was confused about the situation and could not recognise his parents. This episode lasted for about 6 h and symptoms resolved slowly. The migraine headache did improve with intravenous acetaminophen and, after 12 h, the patient no longer complained about headache. An MRI of the brain 3 h after symptom onset and an EEG 12 h after attack onset were normal. The patient’s mother, who was also suffering from migraines, reported a similar attack including speech disturbances associated with disorientation.
A continuous follow-up of this patient revealed rather mild migraine with aura with one headache attack per month in the last 2 years. No other confusional episode occurred. On one occasion, he developed aura symptoms with dysphasia and hemiparesis lasting for 30 min before headache.
Case 10
A 22-year-old patient suffered from migraine with aura since childhood. She was admitted to the emergency department of a local hospital twice because of a confusional state with agitation and incoherent speech following the onset of typical migraine headaches. On admission, she showed disorientation in time and space and reduced spontaneous speech. Otherwise, the neurological examination was normal. Because of increasing agitation, sedation was necessary for cranial CT scan with contrast agent and a spinal tap. Results of these examinations were within normal limits. Within 24 h, the headaches subsided and the patient recovered completely. An MRI of the brain and an EEG performed after the first episode were also normal.
Discussion
Acute confusional migraine is considered a rare migraine variant primarily seen in children and adolescents. In all of our patients, the syndrome is comparable with ACM that has been described for paediatric patients; in none has an underlying disorder been found.
In line with previous reports (4,8–11), disorientation, memory problems, difficulty in recognising familiar people, and speech disturbance were frequently observed in our patients. As in the literature, the confusional state usually lasted for several hours (3,12). Also in accordance with the literature (10,12), recurring confusional episodes were observed in several of our patients (n = 7). In contrast to some reports, agitation (3) and amnesia (4,11,13) were not major symptoms in most of our patients. Also, the frequent association with mild head trauma as a trigger (3) was less consistent in our series. Case 7 had suffered from a polytrauma, but head trauma was not considered as a direct trigger for the individual confusional episode. Two patients (Cases 1 and 9) were playing soccer, but no head trauma was reported. Two of our patients appeared to have apraxia, which has not been reported in the context of ACM. Recently, however, apraxia was described as a complex aura symptom (14). As episodes were fully reversible after hours in our patients, neuropsychological testing could not be performed in the emergency setting. Interictal neuropsychological testing was performed in Case 2. She showed discrete short-term memory deficiency probably attributable to perinatal damage.
Clinical features and investigations of patients with acute confusional migraine
Temporal relation of confusion and headache is indicated by X in the column “before, during, after headache”.
Abbreviations: MwoA = Migraine without aura, MwA = Migraine with aura, n.a. = not available, hx = history (occurred in earlier attacks, not associated with confusion), # these patients were playing soccer at symptom onset, but no head trauma was reported.
Ictal investigations are scarce as the prevalence of ACM is probably as low as 0.4% in children (10). Most ictal abnormalities have been found in EEG-studies. Frontal and occipital slowing in the EEG can outlast clinical symptoms in ACM (4,11). In our series, only one EEG was recorded ictally (Case 9), which was normal. In the literature, ictal SPECT showed hypoperfusion in the left splenium of the corpus callosum (11) in one patient and ictal magnetic resonance angiography (MRA) demonstrated reversible narrowing of the left middle and posterior cerebral arteries in another patient (10). In our series, only one patient (Case 9) had MR-angiography during the confusional episode, which was normal.
In the literature, only a few cases of ACM in adults have been published but confusional states have been described in adult patients with CADASIL (5), ‘migrainous syndrome with CSF pleocytosis’ (16,17) and familial hemiplegic migraine (18). Clinical presentation and investigations (Table 2) ruled out any of these conditions in our series. Conditions similar to ACM have been termed ‘benign post traumatic encephalopathy’ in the literature (19). In the context of familial hemiplegic migraine, the term ‘encephalopathy’ was used for patients with severe alterations in consciousness, who subsequently developed aphasia or agitation (20). Those patients also showed MRI abnormalities such as cortical swelling. Therefore, we suggest that ACM might be the most appropriate term for a transient benign disorder that is likely to be a complex aura phenomenon, whereas ‘migraine encephalopathy’ might be preferred in the context of trauma or in association with alterations of consciousness and/or abnormalities in imaging or other investigations.
The main differential diagnoses of ACM are epileptic seizures, vascular disorders, encephalitis, and intoxication. However, the clinical course with remission within hours and its rather typical presentation with migraine headache make it easier to distinguish. Epilepsy is probably the most challenging differential diagnosis for an episodic disorder with focal neurological signs, headache and confusion. This topic has been reviewed elsewhere (21).
Conclusions
Based on this series of patients, we suggest expanding the concept of confusional migraine from the paediatric population to adults. The temporal course of the confusion as well as the association with visual and other aura symptoms suggest cortical spreading depression as the underlying pathophysiology. Confusional migraine should be added to the International Classification of Headache disorders (22) as a subtype of migraine with aura.
Footnotes
Acknowledgement
Andreas R. Gantenbein and Franz Riederer contributed equally to this work.