Understanding Protein Protocadherin-19 (PCDH19) Syndrome: A Literature Review of the Pathophysiology.

PCDH19 syndrome is a monogenic epilepsy related to the protein protocadherin-19 (PCDH19) gene, which encodes for a protein important for brain development. The protein also seems to regulate gamma-aminobutyric acid type A receptors (GABA(A)(R)). The disease presents with refractory epilepsy that is characterized by seizures occurring in clusters. Till now, the pathophysiology of the disease is mainly unknown, so we conducted a literature review to elucidate the pathophysiology of PCDH19-related epilepsy. We used two databases to investigate this literature review (Google Scholar and PubMed). We selected full-text papers that are published in the English language and published after the year 2000. We selected initially 64 papers and ended up with 29 to conduct this literature review. We found four main theories for the pathophysiology of PCDH19-related epilepsy: GABA(A)(R) dysregulation, blood-brain barrier (BBB) dysfunction, cellular interference, and the AKR1C1-3 gene product deficiency. GABA(A)(R) dysfunction and expression cause decreased effective inhibitory currents predisposing patients to epilepsy. BBB dysfunction allows the passage of methyl-D-aspartate (NMDA)-type glutamate receptor antibodies (abs-NR) through the BBB susceptible membrane. The cellular interference hypothesis establishes that the mutant and non-mutant cells interfere with each other's communication within the same tissue. Women are more susceptible to being affected by this hypothesis as men only have one copy of the x gene and interference is mediated by this gene, meaning that it cannot occur in them. Finally, downregulation and deficiency of the AKR1C3/AKR1C2 products lead to decreasing levels of allopregnanolone, which diminish the regulation of GABA(A)(R).

Reversible Cerebral Vasoconstriction Syndrome in the Postpartum Period: A Systematic Review and Meta-Analysis.

(1) Background: Reversible cerebral vasoconstriction syndrome (RCVS) encompasses a clinical and radiological diagnosis characterized by recurrent thunderclap headache, with or without focal deficits due to multifocal arterial vasoconstriction and dilation. RCVS can be correlated to pregnancy and exposure to certain drugs. Currently, the data on prevalence of RCVS in the postpartum period is lacking. We aim to investigate the prevalence of RCVS in the postpartum period and the rate of hemorrhagic complications of RCVS among the same group of patients; (2) Methods: We conducted the metanalysis by using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), and Meta-Analyses and Systematic Reviews of Observational Studies in Epidemiology (MOOSE) protocol. To analyze the Bias, we used the Ottawa Newcastle scale tool. We included only full-text observational studies conducted on humans and written in English. We excluded Literature Reviews, Systematic Reviews, and Metanalysis. Additionally, we excluded articles that did not document the prevalence of RCVS in the postpartum period (3). Results: According to our analysis, the Prevalence of RCVS in the postpartum period was 129/1083 (11.9%). Of these, 51/100 (52.7%) patients had hemorrhagic RCVS vs. 49/101 (49.5%) with non-hemorrhagic RCVS. The rates of Intracerebral Hemorrhage (ICH) and Subarachnoid Hemorrhage (SAH) were (51.6% and 10.7%, respectively. ICH seems to be more common than.; (4) Conclusions: Among patients with RCVS, the prevalence in PP patients is relativity high. Pregnant women with RCVS have a higher recurrence of hemorrhagic vs. non-hemorrhagic RCVS. Regarding the type of Hemorrhagic RCVS, ICH is more common than SAH among patients in the postpartum period. Female Sex, history of migraine, and older age group (above 45) seem to be risk factors for H-RCVS. Furthermore, recurrence of RCVS is associated with a higher age group (above 45). Recurrence of RCVS is more commonly idiopathic than being triggered by vasoactive drugs in the postpartum period.

Prevalence of Fabry Disease in Patients With Cryptogenic Strokes: A Systematic Review.

Fabry disease (FD) is an X-linked disorder involving multiple organs. Stroke is a serious and frequent complication of FD. Cryptogenic stroke is a common presentation of FD, especially in the young population. The etiology of cryptogenic stroke is highly variable and difficult to assess, frequently leaving patients without a primary diagnosis. We conducted a systematic review to investigate the pooled prevalence of FD among patients with cryptogenic stroke, or patients with FD in whom a stroke was the presenting condition. English-language studies involving humans published in the last 20 years were included in this systematic review. FD was more common in male patients and tended to present at an earlier age. The frequency of hemorrhagic and ischemic strokes in this population was similar to that in the general population. There was a high rate of stroke recurrence in the study sample, even among patients undergoing enzyme replacement therapy. We conclude that screening for FD in patients with cryptogenic stroke is low yield and not cost-effective. However, it may be worthwhile to screen for FD among patients with recurrent strokes.

Understanding Parinaud's Syndrome.

Parinaud's syndrome involves dysfunction of the structures of the dorsal midbrain. We investigated the pathophysiology related to the signs and symptoms to better understand the symptoms of Parinaud's syndrome: diplopia, blurred vision, visual field defects, ptosis, squint, and ataxia, and Parinaud's main signs of upward gaze paralysis, upper eyelid retraction, convergence retraction nystagmus (CRN), and pseudo-Argyll Robertson pupils. In upward gaze palsy, three structures are disrupted: the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF), interstitial nucleus of Cajal (iNC), and the posterior commissure. In CRN, there is a continuous discharge of the medial rectus muscle because of the lack of inhibition of supranuclear fibers. In Collier's sign, the posterior commissure and the iNC are mainly involved. In the vicinity of the iNC, there are two essential groups of cells, the M-group cells and central caudal nuclear (CCN) group cells, which are important for vertical gaze, and eyelid control. Overstimulation of the M group of cells and increased firing rate of the CCN group causing eyelid retraction. External compression of the posterior commissure, and pretectal area causes pseudo-Argyll Robertson pupils. Pseudo-Argyll Robertson pupils constrict to accommodation and have a slight response to light (miosis) as opposed to Argyll Robertson pupils were there is no response to a light stimulus. In Parinaud's syndrome patients conserve a slight response to light because an additional pathway to a pupillary light response that involves attention to a conscious bright/dark stimulus. Diplopia is mainly due to involvement of the trochlear nerve (IVth cranial nerve. Blurry vision is related to accommodation problems, while the visual field defects are a consequence of chronic papilledema that causes optic neuropathy. Ptosis in Parinaud's syndrome is caused by damage to the oculomotor nerve, mainly the levator palpebrae portion. We did not find a reasonable explanation for squint. Finally, ataxia is caused by compression of the superior cerebellar peduncle.

Understanding Seizures and Prognosis of the Extreme Delta Brush Pattern in Anti-N-Methyl-D-Aspartate (NMDA) Receptor Encephalitis: A Systematic Review.

Anti-N-methyl-d-aspartate (NMDA) receptor encephalitis (ANMDARE) is an autoimmune disorder with neurological and psychiatric features. The disease presents with a viral prodrome, followed by psychiatric manifestations. In the next phase, movement disorders or/and seizures occur. Finally, in the last phase, there is a decrease in the level of consciousness. Central hypoventilation and autonomic dysfunction can occur. Recently a unique EEG (electroencephalogram) pattern has been associated with anti-NMDA receptor encephalitis, the extreme delta brush (EDB). Although the association of the EDB with ANMDARE is known by the medical community, its significance is mainly unknown. A systematic review on NMDARE is also scarce. We decided to conduct a systematic review on this topic to consolidate the knowledge and establish the importance of the EDB as a prognostic factor. To conduct this systematic review, we used only studies conducted in humans, written in English, and published in the last 20 years. We used PubMed as a database and searched the following search terms: ("NMDA encephalitis"[Title/Abstract] AND "Epilepsy"[Title/Abstract]) OR (NMDA encephalitis"[Title/Abstract] AND "seizures" [Title/Abstract]) OR ("NMDA encephalitis"[Title/Abstract] AND "extreme delta brush"[Title/Abstract]). The protocol used for this systematic review was the Meta-analyses Of Observational Studies in Epidemiology (MOOSE) protocol, and to analyze the bias of the studies, we used the ROBINS-1 tool. Eight studies were collected from our search strategy. Our data pulling showed that seizures were present in 178/249 (71.48%) patients. Status Epilepticus was reported in 29/96 (30.20%), and the EBD was seen in 30.89% (55/178) patients with seizures. The range of EDB was 5.9%-33% among the studies. Because the sample size was small, the statistical power was decreased. We had a low overall risk of bias. The wide range in the results could be related to the timing of the EEG recording. EDB was associated overall with increased length of hospital stay, increased ICU admission, and incidence of status epilepticus. The etiology of the EDB remains mainly unknown. However, it has been postulated that in NMDAR encephalitis, there is a disruption of the rhythmic neuronal activity. When antibodies block/target the NMDAR, the rhythmic neuronal activity is disrupted, leading to the unique EDB pattern. Another theory suggests that delta activity is caused because of focal abnormalities in the brain, and the superimposition of the beta waves is related to the alterations of the NMDA receptors.

Crimean-Congo Hemorrhagic Fever Beyond Ribavirin: A Systematic Review.

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne virus endemic to a vast geographical area spanning from Africa to the shores of the Mediterranean Sea and north to the Balkans. The infection carries a high case fatality rate, which prompts the development of new treatment and prophylactic measures. This review explores the different treatment and prophylactic measures found in recent literature. For this purpose, we used Medical Subject Headings (MeSH) as well as PubMed advanced search. The inclusion criteria included full-text studies conducted on humans and in the English language. We found that plasma exchange was associated with a decrease in mortality rates. Similarly, the use of immunoglobulins proved effective in decreasing the severity and mortality risk. Ribavirin use was determined as a post-exposure prophylaxis drug with no statistically significant difference in oral or intravenous routes of administration. More studies should be conducted on CCHF as the number of outbreaks and endemic areas seem to be on the rise. For the time being, supportive therapy along with adjuvant antivirals appear to be the main course of management of CCHF. However, the need for definitive therapeutic agents and guidelines is warranted.