Week 3 Discussion Answers
The following disorders are unique genetic neurological disorders that result in varied clinical presentations and outcomes for patients.
Neurofibromatosis divided into type one (NF1) and type 2 (NF2) are autosomal dominant neurocutaneous disorders that results in altered genes that causes dysregulation of tumor suppression (Defendi, 2022). NF1 is more common and occurs in one out of every 3,500 births (Germanwala, n.d.). NF1, there is a deletion of the NF1 gene that produces neurofibromin 1 that activates the protein ras-GTPas which is involved with cellular signal transduction (Defendi, 2022). Without the NF1 gene there is an overactive ras-GTPas resulting in the activation of other proteins, in turn activating genes for cell growth and differentiation leading to benign or malignant tumors (Defendi, 2022). Common benign tumors include cutaneous neurofibromas, plexiform neurofibromas and optic nerve gliomas (Defendi, 2022). Patients with NF1 present with a family history of the disorder, six or more of the café-au-lait spots on the skin, freckling in the underarms and groin, presence neurofibromas (about pea-sized) on or just under skin, plexiform neurofibromas, Lisch nodules, skeletal abnormalities and have the potential for tumors on the optic nerve (Germanwala, n.d.). Additionally, these patients may present with macrocephaly, short stature, are at risk for seizures, learning disabilities, speech issues and hyperactivity (Germanwala, n.d.).
Cri-du-chat syndrome is a chromosomal disorder, also known as 5p minus syndrome where there is a deletion of the variable size on the short arm of chromosome 5 (Mainardi, 2006). Since this disorder is a syndrome, there are several clinical features that are common in the presentation of this disorder including microcephaly, large nasal bridge, hypertelorism, epicanthal folds, downward slanting palpebral fissures, down-turned corners of the mouth, low-set ears, micrognathia, abnormal dermatoglyphics and the hallmark high-pitched cry (Mainardi, 2006). The cry is a result of structural abnormalities of the larynx caused by laryngeal hypoplasia and central nervous system (Lal, 2021). The central nervous system deficit is noted in the “…clivus region of the cranial base with the laryngeal region from which the characteristic cry derived” (Lal, 2021). Neurologically, these patients have developmental and psychomotor delay, with varied levels of abilities. Patients also present with hypotonia which progresses to hypertonia with age. On magnetic nuclear resonance imaging, brainstem atrophy has been noted including the pons, cerebellum, median cerebellar peduncles and cerebellar white matter” (Mainardi, 2006).
Tay-Sachs Disease also known as GM2 gangliosidosis, is a fatal autosomal recessive disorder caused by the HexA gene found on chromosome 15 (McCance & Huether, 2014). The deficiency in the lysosomal enzyme hexosaminidase A (HexA) results in decreased degradation in GM2 gangliosides or fatty acids within nerve cell lysosomes (McCance & Huether, 2014). This build up results in toxic levels of GM2 gangliosides in the neurons throughout the body resulting in misshaped neurons and microglial cells (McCance & Huether, 2014). Leading to cystic degeneration of the cerebral white matter, atrophy of the cerebellar hemispheres and changes in the spinal cord (McCance & Huether, 2014). This disorder in patients presents in infants between three to six months of ages with noted loss of milestones with an overactive startle response (McCance & Huether, 2014). Other signs and symptoms include hypotonia, hyporeflexia, muscle rigidity, blindness and increased head circumference (McCance & Huether, 2014).
Early onset Parkinson’s Disease or Juvenile parkinsonism (JP) is parkinsonian signs and symptoms prior to 21 years. “Levodopa-responsive juvenile parkinsonism that is consistent with diagnostic criteria for Parkinson’s disease is most often caused by mutations in the PARK-Parkin, PARK-PINK1, or PARK-DJ1 genes (Niemann & Jankovic, 2019). The overall pathophysiology is not understood, but it is clear in the body of research that there is a clear relationship between these genes that impact mitochondrial function and oxidative stress response (Cookson, 2012). Most JP patients do not meet the diagnostic criteria for Parkinson’s Disease. Instead, they present with “…disproportionate severity of another movement disorder (e.g., dystonia, ataxia, spasticity), early cognitive decline, severe behavioral disturbance, or relevant medical history such as exposure to dopamine receptor blocking agents (DRBA), head trauma, brain tumor, and other secondary causes” (Niemann & Jankovic, 2019).
Overall, these disorders reflect the complexities of our genetics and our nervous system. It was evident throughout my research that couples with any knowledge of familial history of any genetic disorders should consider genetic counseling prior to having children.
Cookson M. R. (2012). Parkinsonism due to mutations in PINK1, parkin, and DJ-1 and oxidative stress and mitochondrial pathways. Cold Spring Harbor perspectives in medicine, 2(9), a009415. https://doi.org/10.1101/cshperspect.a009415
Defendi, G. L., MD. (2022, October 10). Genetics of Neurofibromatosis Type 1 and Type 2: Overview, NF Genes, Genetic Testing. https://emedicine.medscape.com/article/950151- overview
Germanwala, A. (Ed.). (n.d.). Neurofibromatosis – Symptoms, Diagnosis and Treatments. American Association of Neurological Surgeons. https://www.aans.org/en/Patients/Neurosurgical-Conditions-and- Treatments/Neurofibromatosis
Lal, M. K., MD. (2021, March 7). Cri-du-chat Syndrome: Practice Essentials, Pathophysiology, Epidemiology. https://emedicine.medscape.com/article/942897-overview
Mainardi, C. P. (2006, September 5). Cri du Chat syndrome – Orphanet Journal of Rare Diseases. BioMed Central. https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-1-33
Niemann, N., & Jankovic, J. (2019). Juvenile parkinsonism: Differential diagnosis, genetics, and treatment. Parkinsonism &Amp; Related Disorders, 67, 74–89. https://doi.org/10.1016/j.parkreldis.2019.06.025
McCance, K.L. & Huether, S.E. (Eds.). (2014). Pathophysiology: The biologic basis for disease in adults and children. (7th. ed.). Elsevier Mosby. https://online.vitalsource.com/books/9780323088541
· Discuss the pathophysiology of cerebrovascular accidents (CVAs)—thrombotic, embolic, hemorrhagic, and lacunar—their incidence and prevalence, clinical manifestations, evaluation, and treatment. P. 598
Pathophysiology of cerebrovascular accidents (CVAs) is any abnormality or blockage of blood flow to the brain leading to a stroke. There are different types of strokes along with different areas where strokes can take place in the brain leading to different neurological deficits in the patient (McCance & Huether, 2014).
A thrombotic stroke is where thrombi have formed within the arteries or intracranial vessels supplying the brain. An embolic stroke is when an embolus has formed outside the brain and travels to the brain via the bloodstream. Thrombotic and embolic strokes, also known as ischemic strokes are the most common, accounting for 87% of the strokes that occur (McCance & Huether, 2014).
The clinical manifestations of a thrombotic or embolic stroke are contralateral hemiparesis or hemiplegia, expressive aphasia, and dysphagia, hemianopia and quardranopsia. A simple screening tool for clinical manifestations of a stroke is BE-FAST. Balance, Eyes, Face, Arm, Speech, Time.
“Time is brain” is the classic saying when dealing with the evaluation and treatment of thrombotic and embolic stroke. Restoring brain perfusion is the number one priority followed by preventing recurrent strokes from happening. Treatment consists of recognizing the signs and symptoms of a stroke early on. Once diagnostic imaging such as a Cat scan of the head, has taken place and the type of stroke has been determined, the patient will either receive tissue plasminogen activator (TPA) if not contraindicated, to break down the clot or be taken to the operating room for surgical clipping or craniotomy if the stroke is hemorrhagic.
Hemorrhagic stroke is when a blood vessel within the brain spontaneously begins to bleed. This is the third most common stroke (McCance & Huether, 2014) Priority treatment for hemorrhagic strokes is to stop the bleeding, prevent rebleeding and hematoma enlargement, control intracranial pressure, control vasospasms, Seizure prophylaxis is implemented due to damage in the brain as a result of the stroke.
Lacunar strokes are also a type of ischemic stroke where the infarct is very small and blockages are found deep within the brain structures such as the thalamus or basal ganglia. Lacunar strokes account for 15%-25% of ischemic strokes.