First Report Published of Batten and Moyamoya Diseases Occurring in Same Patient

A patient with both Batten disease and Moyamoya disease — a condition where blood vessels in the skull become obstructed or narrowed, restricting blood flow to the brain — has been described in the first published case of these two conditions occurring in one person.

The case report, “Moyamoya and progressive myoclonic epilepsy secondary to CLN6 homozygous mutation – A previously unreported association,” was published in Epilepsy & Behavior Reports.

The case involves a male patient who, at 16 years old, experienced two tonic-clonic seizures while asleep. At the time, he had no prior history of seizures — he had a mild upper limb tremor, but no other remarkable symptoms or medical history.

Brain imaging at the time did not identify any abnormalities. After another seizure over a year later, the patient was started on sodium valproate (brand names Depakote and Epilim, among others), an anticonvulsant.

He continued to experience seizures every few months — at first, these only occurred during sleep, but later, seizures happened when he was awake, too. His limb tremor got worse, and other symptoms appeared.

“He described his legs as feeling ‘like jelly’ with occasional falls,” the researchers wrote. “He also noticed general cognitive slowing, fatigue and effortfulness when engaging in conversations with people less well known to him.”

Initially, it was suspected that some of these symptoms could be medication side effects, so he was switched to another seizure medication — levetiracetam (brand names Keppra, Spritam, among others) — but it did not alleviate his symptoms.

The patient underwent further evaluation at 20 years old. At this time, MRI revealed some brain volume loss, but other assessments were unremarkable. He was referred for physical therapy, which lessened symptoms somewhat — however, they continued to progress.

By age 22, the patient required a wheelchair to get around, his voice had developed a stutter, and he was unable to cut up food or write legibly. Seizures also became more frequent, occurring about once a week. Additionally, he consistently experienced myoclonus — sudden, jerky muscle contractions.

He went to the hospital for more intensive examination, which led to a suspected diagnosis of progressive myoclonic epilepsy — a form of epilepsy characterized by myoclonus and by seizures that get worse over time.

An initial genetic analysis did not yield remarkable findings. However, the patient then underwent whole-genome sequencing, which revealed mutations in both copies (one inherited from each biological parent) of the CLN6 gene.

Mutations in this gene are known to cause Batten disease, which, in turn, is a known cause of progressive myoclonic epilepsy. These results confirmed the diagnosis of adult-onset Batten disease, or Kufs disease, which is a form of the disorder that does not affect vision.

Repeat brain imaging showed the same loss in brain volume previously detected, but there were also formerly unseen changes indicative of alterations in the brain’s blood vessel system. Further examination revealed abnormal narrowing of several blood vessels that supply blood to the brain.

“The features were in keeping with intradural arterial occlusive vasculopathy/Moyamoya disease,” the researchers wrote. “This is the first report of Moyamoya in the context of neuronal ceroid lipofuscinosis.”

After this finding, the patient was started on blood pressure medication (amlodipine and a statin), without a change in symptoms. Further examination of the patient is continuing.

It is not presently clear whether the patient’s Moyamoya disease is related to the Batten disease; however, there may be a biological rationale to suspect such an association. Specifically, Moyamoya disease is known to occur in contexts of increased inflammation, and Batten disease is characterized by elevated inflammation.

As such, it is, “not unreasonable to suspect that the observed mutations in CLN6 may have played a role in the pathogenesis [of Moyamoya disease],” the researchers wrote.