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.
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