Signs and symptoms
FHM signs overlap significantly with those of migraine with aura. In short, FHM is typified by migraine with aura associated with hemiparesis, and in FHM1, cerebellar degeneration, which can result in episodic or progressive ataxia. FHM can also present with the same signs as benign familial infantile convulsions and alternating hemiplegia of childhood. Other symptoms are altered consciousness (in fact, some cases seem related to head trauma), gaze-evoked nystagmus, and coma. Aura symptoms, such as numbness and blurring of vision, typically persist for 30–60 minutes, but can last for weeks to months. An attack resembles a stroke, but unlike a stroke, it resolves in time. These signs typically first manifest themselves in the first or second decade of life. Causes
See the equivalent section in the main migraine article. FHM mutations are believed to lead to migraine susceptibility by lowering the threshold for cortical-spreading-depression generation. The FHM1 and FHM3 mutations occur in ion channels expressed in neurons. These mutations may lead to both the hyper- and hypoexcitable neurons that might underlie cortical-spreading-depression. How the mutations seen in FHM2 patients might lead to FHM symptoms is even less clear, as the gene mutated in FHM2 is expressed primarily in astrocytes. One proposal states that the depolarization of astrocytes caused by haploinsufficiency of the ATP1A2 Na+/K+-ATPase causes increased release of compounds such as adenosine from astrocytes. These compounds then interact with neighboring neurons, altering their excitability and leading to cortical-spreading-depression and migraine.
Other genetic associations
A fourth gene associated with this condition is the proline-rich transmembrane protein 2 (PRRT2 gene) - an axonal protein associated with the exocytosis complex.A fifth gene associated with this condition is SLC4A4, which encodes the electrogenic NaHCO3 cotransporter NBCe1. Diagnosis
Diagnosis of FHM is made according to these criteria:
Two attacks of each of:Aura with motor weakness accompanied by either reversible visual symptoms (flickering lights, spots, lines, etc. ), reversible sensory symptoms (pins and needles, numbness, etc.) or speech symptoms
At least two occurrences of:One or more aura symptoms that develop over at least 5 minutes
These symptoms lasting more than 5 minutes and less than 24 hours
Headache beginning within 60 minutes of aura onset: These headaches can last 4–72 hours, occur on only one side of the head, pulsate, be of moderate to severe intensity, and may be aggravated by common physical activities such as walking. These headaches must also be accompanied by nausea/vomiting, phonophobia (avoidance of sound due to hypersensitivity), and/or photophobia (avoidance of light due to hypersensitivity).At least one close (first- or second-degree) relative with FHM
No other likely causeSporadic forms follow the same diagnostic criteria, with the exception of family history. In all cases, family and patient histories are used for diagnosis. Brain-imaging techniques, such as MRI, CAT scan, and SPECT, are used to look for signs of other familial conditions such as CADASIL or mitochondrial disease, and for evidence of cerebellar degeneration. With the discovery of causative genes, genetic sequencing can also be used to verify diagnosis (though not all genetic loci are known).