Spectrum of complicated migraine in children: A common profile in aid to clinical diagnosis

Table 1 Represents the very first 3 out of 11 sections of the International Headache Society Classification, the third Edition, 2013[4]

1 Migraine

1.1 Migraine without aura

1.2 Migraine with aura

1.2.1 Migraine with typical aura

1.2.1.1 Typical aura with headache

1.2.1.2 Typical aura without headache

1.2.2 Migraine with brainstem aura

1.2.3 Hemiplegic migraine

1.2.3.1 Familial hemiplegic migraine

1.2.3.1.1 Familial hemiplegic migraine type 1

1.2.3.1.2 Familial hemiplegic migraine type 2

1.2.3.1.3 Familial hemiplegic migraine type 3

1.2.3.1.4 Familial hemiplegic migraine, other loci

1.2.3.2 Sporadic hemiplegic migraine

1.2.4 Retinal migraine

1.3 Chronic migraine

1.4 Complications of migraine

1.4.1 Status migrainosus

1.4.2 Persistent aura without infarction

1.4.3 Migrainous infarction

1.4.4 Migraine aura-triggered seizure

1.5 Probable migraine

1.5.1 Probable migraine without aura

1.5.2 Probable migraine with aura

1.6 Episodic syndromes that may be associated with migraine

1.6.1 Recurrent gastrointestinal disturbance

1.6.1.1 Cyclical vomiting syndrome

1.6.1.2 Abdominal migraine

1.6.2 Benign paroxysmal vertigo

1.6.3 Benign paroxysmal torticollis

Table 2 Lists the frequency of the individual syndromes of complicated migraine reported by the select retrospective studies[7-9]

Study type	Ref.	No. of patients	Frequency of the individual syndromes of complicated migraine reported
Retrospective	[7]	111	Migraine variants 24.3%, basilar type migraine 6.3%, benign paroxysmal vertigo (5.4%), hemiplegic migraine (3.6%), acute confusional migraine (2.7%), benign paroxysmal torticollis (2.7%), typical aura without headache (1.8%), abdominal migraine (1.8%), Alice in Wonderland syndrome (0.9%), ophthalmoplegic migraine (0.9%), and cyclical vomiting (0.9%)
Retrospective	[8]	674	Migraine variants 5.6%, abdominal migraine 39%, benign paroxysmal vertigo 38%, confusional migraine 13%, aura without migraine 9%, paroxysmal torticollis 5%, and a single child with cyclic vomiting
Retrospective, adults in Hyperacute Stroke Units	[9]	375	Conditions other than stroke 31%, which included 22% migraine, 14% functional neurological disorder, 12% syncope, and 6% seizure. In contrast to stroke patients, they tend to be younger, likely to have a brain MRI performed, and had a shorter length of hospital stay

This should be noted that no alternating hemiplegia of childhood and retinal migraine were reported in these studies. MRI: Magnetic resonance imaging.

Table 3 Lists the common clinical characteristics of complicated migraine

	Clinical characteristics
Presenting feature	Any neurologic sign or symptom other than headache
Age	Commonly, but not limited to, occurs during infancy and childhood
Sex	Boys dominate in migraine variants and girls dominate in the rest of the complicated migraine other than migraine variants
Onset	Acute or sudden but relatively slower than seizure
The context	Patients may have past episode of similar or different symptomatology suggesting migraine attack
Modifying factor	Unlike migraine, none
Family history	Unlike common migraine, in complicated migraine a family history of migraine is almost always present
Course	Transient, may occur once in lifetime or may become episodic but always reversible with the exception to alternating hemiplegia
Examination	With few exceptions, particularly between the episodes, neurologic examination is almost always normal
Differential diagnosis: common/rare	Partial seizures, seizure like activity, transient ischemic attack/migraine like syndrome1 and acute stroke
Investigation	Usually normal including neuroimaging and electroencephalography
Diagnosis	A short course of the presenting symptom between seizure and common migraine defines the complicated migraine

¹Migraine like syndrome includes aseptic meningitis, pseudotumor cerebri, subarachnoid hemorrhage, sinus venous thrombosis, arteriovenous malformation, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes, and rarely brain tumor. Complicated migraine is not a single entity. It includes a variety of individual clinical syndromes. The propose common clinical profile in add to clinical diagnosis of complicated migraine is quite distinct from other conditions like migraine with and without aura, seizure, and migraine like syndromes. To represent collectively such a large subgroup of the individual syndromes, the term complicated migraine has been used in this review.

Table 4 Lists the diffrential diagnosis of migraine like syndromes, their presenting symptoms, and the confirmatory laboratory tests

Migraine like syndrome	Presenting symptom	Confirmed by
Aseptic meningitis	Infants and children age < 5 yr presenting with constitutional symptoms together with meningeal signs	Cerebrospinal fluid study molecular testing by polymerase chain reaction[28]
Pseudotumor cerebri	Persistent headache with prominent visual symptoms and head tilt	An increased intracranial opening pressure measured in calm patient with straight leg position
Subarachnoid hemorrhage	Waxing and waning levels of consciousness, apnea, bradycardia before seizure	Brain computerized tomography and/or presence of blood or xanthochromic cerebrospinal fluid
Sinus venous thrombosis	Altered mentation with no obvious etiology or no seizures	Brain computerized tomography with and without contrast or MRV
Arteriovenous malformation	Sensory cutaneous aura with or without seizure or headache	MRA and MRV or computerized tomographic angiography
MELAS	Early symptoms, muscle weakness and pain, recurrent headaches, loss of appetite, vomiting, and seizures	MRI of the brain mimicking acute migrainous stroke but differs by having no respect to a specific cerebral arterial vascular territory
Brain tumor	Progressively worsening headache with onset of focal neurologic sign or seizure	Computerized tomography with contrast or MRI of the brain with and without contrast

The headache recurrent or persistent may be the presenting sign of migraine like syndromes except sinus venous thrombosis and subarachnoid hemorrhage. Their initial presentation is waxing and waning level of consciousness. MRV: Magnetic resonance venography; MRA: Magnetic resonance angiography; MELAS: Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes; MRI: Magnetic resonance imaging.

Table 5 Shows select cerebrospinal fluid biochemical changes which help to distinguish between bacterial meningitis, aseptic meningitis, and migraine attacks[34-39]

Increased level in cerebrospinal fluid	Comments
Lactate	> 3.5 mmol/L is a good predictor of bacterial meningitis[34]
Procalcitonin	> 0.5 ng/mL is a good predictor of bacterial meningitis[35]
Ferritin	106.39 +/- 86.96 ng/ dL (n = 24) was considerably higher than the viral meningitis group (10.17 +/- 14.09, P < 0.001)[36]
Cytokines	Children with mumps meningitis (n = 19), echovirus 30 meningitis (n = 22), with comparison to children without meningitis (n = 21)[37]
Glutamic acid	An excess of neuroexcitatory amino acids during migraine attacks supports a state of neuronal hyperexcitability[38]
5-hydroxyindoleacetic acid	Level was higher in migraine than the controls[39]

Cerebrospinal fluid and systemic biochemical changes in migraine are complex, contradictory, and often unreplicated. Generally accepted CSF changes are as follows: (1) Changes in neuroexcitatory amino acids and magnesium; (2) Changes of vasoactive peptides in trigemino-vascular system; (3) Catecholaminergic changes suggesting sympathetic over activity; (4) Alterations in methionine-encephalin levels; and (5) Systemic changes include derangement of 5-Hydroxytryptophan metabolism hormonal fluctuations in female to precipitate migraine attack[40]. CSF: Cerebrospinal fluid.

Table 6 List the select reports of the use of multimodaility and their results primarily in children with prolonged hemiplegic migraine[42-45]

Neuroimaging type and the clinical conditions	Study revealed
Multimodality neuroimaging in a single familial hemiplegic migraine[42]	Cytotoxic edema along with evidence of hypometabolism but no evidence of hypoperfusion of the affected cerebral hemisphere
Perfusion- and susceptibility-weighted imaging in a 13-year-old-female 3 h after the right hemiplegia[43]	Hypoperfusion in the left cerebral hemisphere and a matching prominent hypotensity, respectively. Diffusion tensor imaging sequences were normal. These abnormalities completely resolved 24 h after the attack onset
Perfusion- and diffusion-weighted MRI during visual auras in four migraineurs[44]	Cerebral blood flow and volume, both decreased by 16%-53% and 6%-33%, respectively. Mean transit time in the affected occipital cortex was increased by 10%-54%. No changes in the diffusion coefficient were observed during and after the resolution of the visual aura
Brain MRI in six population and 13 clinic-based meta-analysis studies in migraines with and without aura[45]	White matter abnormalities, silent infarct-like lesions, and volumetric changes in both gray and white matter regions were more common in migraineurs than in control groups. These data suggest that migraine may be a risk factor for structural changes in the brain

Some of these conflicting reports support the clinically observed variability in the manifestation of the migraine. MRI: Magnetic resonance imaging.