Discussion:
PDA is a rare neurological manifestation of acquired conditions or
hereditary disorders, like autosomal dominant episodic dysarthria and
truncal ataxia.5 It is a well-described phenomenon in
multiple sclerosis since 1980, yet one of the least common paroxysms
encountered in clinical practice.2 Midbrain has a
pivotal role in PDA symptomatology, as Matsui et al. observed with
lesions near or within the red nucleus of the midbrain disturbing the
crossed fibers of cerebello-thalamocortical pathways in the lower
midbrain, connecting cerebellum and cortex via the superior cerebellar
peduncle. 4,5
Pathophysiology of PDA is not fully known to date, and it has been
reported in many autoimmune diseases, namely, antiphospholipid syndrome
and Behcet’s disease. 5,4 Behcet’s syndrome is
characterized by widespread vasculitis involving arteries and venules
without preference to a specific size. Hence its variable clinical
phenotypic presentations, and highly correlated with the geographical
distribution of HLA-B51. 1,2 NBS has a distinctive
lesion pattern, described in the literature as cascade sign, due to
extension of brain lesions from thalamus / Meso-diencephalon and
telencephalon to the brainstem, differentiating it from
inflammatory-demyelinating disease such as multiple sclerosis (MS).
Naci Kocer et al. In a study of 65 patients with NBS, demonstrated
intra-axial veins and small vessels pattern on MRI head; commonly, the
meso-diencephalic junction (MDJ) in 46% of patients, followed by
Ponto-bulbar region in (40%), the hypothalamic-thalamic region (23%),
basal ganglia in 2%, followed by telencephalon, cerebellum in three,
and the cervical cord.1 Such finding; support venular
involvements and supports their hypothesis of small vessel vasculitis.1 Xia et al. and Codeluppi et al. in a case report and
case report of two patients respectively demonstrated PDA and solitary
sclerosis of the midbrain with positive CSF oligoclonal bands,
supporting demyelinating/inflammatory etiology with an adequate response
to Carbamazepine. 3,6
PDA in neuro-Behcet’s disease, theoretically speaking, is expected if
lesions involve the midbrain, as seen in one previously reported case
associated with many lesions in the periventricular white matter and
brainstem correlating with a typical neuroradiological pattern of NBD
fulfilling the NBD diagnostic criteria.6 However,
isolated midbrain lesions in neuro-Behcets manifesting with isolated
midbrain lesion have never been reported, raising possible subtypes of
NBD, for which a better understanding of the disease’s pathophysiology
on a molecular level is warranted. 8
PDA pathogenesis is not fully understood to date, with other variants as
Xia et al. has presented a none-ataxic PDA variant in solitary midbrain
sclerosis. Understanding midbrain PDA triggering lesions; relative to
their burden and nature (vascular, demyelinating, vasculitic) is
paramount, which would aid in better understanding of possible
pathophysiology relevant to cerebello-thalamocortical pathways, and
hence better-targeted treatment. 6
Finally, Carbamazepine has been reported to be effective in PDA-related
MS lesions, solitary sclerosis, and APLS related lesions; by opposing
the Ephaptic transmissions between contiguous fibers.3,5 As previously, Ostermann & Westerberg et al.
postulated that ion channel dysfunction could alter fibers and generate
axon potentials without synapses that could alter the excitability of
neighboring neurons owing to their anatomical and electrical proximity
(Ephaptic transmission). 9 Nonetheless, Carbamazepine
can affect the entire axon membrane and successfully block the Ephaptic
transmission for better PDA control, but other anti-epileptics
(phenytoin, lamotrigine, acetazolamide, and levetiracetam) have been
reported to be effective as well. In our patient, due to idiosyncratic
drug-induced reaction, Carbamazepine cannot be assessed for its
effectiveness but was well controlled on Lacosamide to date.
DECLARATIONS