A case of familial hemiplegic migraine type 1 associated with parkinsonism
A 58-year-old female patient presented to the out-patient department complaining on and off headache which was often accompanied by the weakness in the left side of the body and rarely involved both the sides. She had a known family history of FHM type 1. She was experiencing progressive alterations in gait, stiffness and right-sided resting tremor from last two years.
The most likely diagnosis of this patient would be:
- Sinus headache
- Tension headache
- Chronic progressive headaches
- Hemiplegic migraine
Hemiplegic migraine (HM) refers to the only headache syndrome associated with known genetic mutations, which is indicated by the motor weakness (hemiparesis) associated with aura, including sensory, visual disturbances and dysphasia. Sometimes, the HM may be associated with severe symptoms including seizures, coma, fever, altered mental state and so on. Depending upon the family history, the HM occurs in two main forms, familial hemiplegic migraine (FHM) which is hereditary and sporadic hemiplegic migraine (SHM) which occurs without any such family history of motor weakness during the aura. It is a rare condition affecting one in 10,000 people and the prevalence of FHM and SHM is almost equal. The diagnosis of FHM involves the screening of three genes (CACNA1A, ATP1A2 and SCNA1) involved.1 The onset of FHM usually occurs in the early years of life relative to the onset of typical migraine; however, the frequency of attacks decreases with the increasing age. Typically, almost 50% of FHM type 1 patients have cerebellar signs ranging from nystagmus to late-onset mild ataxia.2 The management of FHM involves similar approaches as that of migraine with aura, except for triptans that are contraindicated in MHF.1 However, the treatments are not reliable; verapamil and acetazolamide have shown positive results.3 Also, the preventive approaches using antiepileptic agents seem promising. 1
The patient had a family history of FHM type 1 and significant cerebellar ataxia. Her deceased mother also had both FHM and parkinsonism, but she was never diagnosed or treated for the same.
Examination and Laboratory Investigations
A physical and neurological examination showed a reduced degree of facial expression, bilateral gaze-evoked horizontal nystagmus (drifted eye), rigidity, slow movement and resting tremor. Moreover, when asked to make antagonistic movements in quick succession and finger tapping, the speed amplitude and regularity was significantly reduced on the left side. The limbs were weakened, especially left side and abnormal walk with a forward-flexed posture was observed. Imaging studies showed an enlarged peri-vascular spaces, and cerebellar atrophy. Also, the signal on T1-weighted MRI was decreased while that on T2-weighted MRI was increased. Moreover, an increased self diffusion was reported in a bilateral globus pallidus.
The typical migraine headache (already started) with aura was treated using di-hydro-ergotamine mesylate (DHE 45; 1 mL intravenously), which reduced the throbbing effects of these headaches. A special attention was paid to towards the weekly dosage of DHE 45 which was not to exceed 6 mL and other interactive drugs were avoided during this treatment. Occasionally, ibuprofen was also prescribed to treat headaches at home and antacid was given concomitantly. In addition, selegiline was prescribed, which reduced the tremor to some extent but had very limited effects on the extra-pyramidal symptoms.
The FHM is the only headache associated with gene alterations and a monogenic mode of inheritance. There are three different genes involved in the pathogenesis of FHM, including CACNA1A, ATP1A2, and SCN1A responsible for FHM type 1, FHM type 2, and FHM type 3, respectively. 4 These gene mutations are believed to affect the Na (+), K (+) ATPase alpha subunit, which may be linked to the rapid-onset dystonia Parkinsonism (RDP), and FHM. More than 40 hereditary changes have been mapped to the human genes, which may be linked to RDP, FHM or different of FHM with neurological symptoms. Earlier, it was reported that specific alleles of ATPalpha are linked to neurological dysfunction, altered locomotion, reduced longevity, and progressive neuro-degeneration.5 Other drugs, including acetazolamide, tricyclic antidepressants, beta blockers, and calcium channel blockers may be warranted for FHM1 frequent attacks.6
Treatment with the DHE 45 injection, ibuprofen (occasionally) and selegiline successfully relieved the symptoms of migraine attacks and Parkinson's disease, respectively. On one-year follow-up, the MRI results turned out to be normal and there were no signs of progression.
- Ducros A. Rev Neurol (Paris). 2008 Mar; 164(3):216-24.
- Roberta A Pagon. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993-2015.
- Black DF. Semin Neurol. 2006 Apr; 26(2):208-16.
- Gallanti A, Cardin V, Tonelli A, et al. Neurol Sci. 2011 May; 32 Suppl 1:S141-2.
- Ashmore LJ, Hrizo SL, Paul SM, et al. Hum Genet. 2009 Sep; 126(3):431-47.
- Jen JC. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015. Available from: ncbi.nlm.nih.gov/books/NBK1388/