|Year : 2016 | Volume
| Issue : 1 | Page : 52-57
Porencephaly: case report and review
P Bhuta1, D Bhalodiya1, U Patel1, A Muley2
1 Resident, Department of Medicine, Sumandeep Vidyapeeth, SBKS MI & RC, Piparia, Vadodara, Gujarat, India
2 Professor, Department of Medicine, Sumandeep Vidyapeeth, SBKS MI & RC, Piparia, Vadodara, Gujarat, India
|Date of Web Publication||29-Aug-2018|
Resident, Department of Medicine, Sumandeep Vidyapeeth, SBKS MI & RC, Piparia, Vadodara, Gujarat
Source of Support: None, Conflict of Interest: None
Porencephaly is an extremely rare disorder of the central nervous system defined as a ‘fluid-filled defect communicating with ventricles or separated from them by a thin layer of brain tissue and covered on the outside by arachnoid’ and is found to be associated with COL4A1 mutation. Its diagnosis depends on demonstrating a well-defined CSF-filled space-occupying lesion communicating with ventricles on CT scan or MRI of brain. There has been no report of porencephaly associated with myesthenia gravis till now. We present a case of porencephaly who presented with altered sensorium and myesthenia gravis to highlight the point that although rare at present, its incidence may increase in future. The best way to contain the increase in incidence of porencephaly is genetic counselling and prenatal testing in affected individuals and those at risk. This will also help in restricting increase in other disorders related to COL4A1 mutation.
|How to cite this article:|
Bhuta P, Bhalodiya D, Patel U, Muley A. Porencephaly: case report and review. J Integr Health Sci 2016;4:52-7
| Introduction|| |
Porencephaly is an extremely rare disorder of the central nervous system. It is defined as a ‘fluid-filled defect communicating with ventricles or separated from them by a thin layer of brain tissue and covered on the outside by arachnoid.‘ Damage to the cerebrum during delivery or as an unnoticed trauma during infancy may present with porencephaly much later in life. It may be a result of trauma, infection or hemorrhage in postnatal life. Hypoperfusion may also cause focal encephalomalacia followed by focal necrosis of gray and white matter and cystic degeneration. Its diagnosis depends on demonstrating a well-defined CSF-filled space- occupying lesion communicating with ventricles on CT scan or MRI of brain.
There have been reports of porencephaly with CO poisoning, cognitive dysfunction, psychosis, CMV infection, dermoid cyst but there has been no report of porencephaly associated with myesthenia gravis till now. We present a case of porencephaly who presented with altered sensorium and myesthenia gravis.
| Case History|| |
An eighteen year old unmarried female belonging to lower socio-economic status presented with altered sensorium in emergency in our hospital. Her mother gave history of two vomiting episodes early in the morning which were non projectile and non foul smelling. There was history of bodyache and headache also. After vomiting the patient developed tightening of all four limbs for about two minutes and also altered sensorium. After this she became unconscious and stopped moving limbs. However, there was no history of uprolling of eye balls, tongue bite, frothing, deviation of angle of mouth, injury during the episode, fever, abdominal pain, hematemesis, diarrhea, head injury, breathlessness, chest pain, snake bite or ingestion of any unknown substance. There was no history of similar episode in the past or delayed development in childhood. There was no history of any other major or chronic illness in the past either, but there was history of ear discharge from both ears on and off since childhood. On examination she was a febrile, her pulse rate was 146/min regular, blood pressure was 146/90 mm Hg in left arm in supine position, respiratory rate was 20/min and spO2 was 85% on O2 at 4 litre/min. She had pallor but there was no icterus, clubbing, cyanosis, edema or lymphadenopathy. Hair and skin appeared to be normal. No scar marks were present.
On systemic examination, there were harsh vesicular breath sounds and tachycardia in otherwise normal respiratory and cardiovascular system. Her GCS (Glass Gow Coma scale) was E1M1V1 so higher functions, cranial nerves and power could not be assessed. There was generalised hypotonia with hyporeflexia in all four limbs. Plantar reflex was not elicitable. Pupils were unequal and sluggishly reacting. Meningeal signs were absent. ABG (Arterial blood gas analysis) revealed respiratory acidosis. The patient was immediately intubated and kept on mechanical ventilation. All her lab reports were within normal limits except increased neutrophil count and respiratory acidosis. Presumptive diagnosis of seizure due to intracranial bleed or infective pathology – meningo encephalitis or encephalitis or pyomeningitis with postictal state was made keeping a possibility of venous sinus thrombosis also. Based on the clinical examination and lab reports antibiotics, antiepileptics and other symptomatic and supportive treatment including mannitol was started.
Next day the patient developed moderate to high grade continuous fever. After two days of treatment, patient gradually became conscious and oriented. She started responding to commands but flaccid quadruparesis persisted with ptosis and nonreacting pupils. This raised a possibility of snakebite or myaesthenia so anti snake venom was given but no improvement was seen. However neostigmine test turned out to be positive suggesting presence of myasthenia gravis. CT scan head revealed presence of porencephalic cyst which was confirmed on MRI.
|Figure 1: CT head revealing frontal cyst communicating with frontal horn of right ventricle|
Click here to view
| Discussion|| |
Porencephaly is a rare congenital disorder of the CNS with a cyst or a cavity filled with cerebrospinal fluid in the brain’s parenchyma., It is usually a result of damage from stroke or infection after birth (more common), but it may also be caused due to abnormal development before birth (which is inherited and less common). The common etiological factors include infections, anoxia and exposure to aggressing factors., These injuries lead to destruction of brain tissue and cavitations which may manifest as multicystic encephalomalacia (MCE) or porencephaly (POR). Insults caused towards the end of pregnancy, during delivery or during the first days of life lead to MCE as they reach an already matured brain able to express differentiated tissue responses. They cause lesions of imprecise limits containing trabeculae with glial reaction of varying degrees.,, Insults occurring at the end of the second or the beginning of the third trimester of pregnancy manifest as POR as they affect an immature brain unable to express significant astrocyte reaction. This results in formation of a smooth walled cavity with defined boundaries and little or no perilesional gliosis.
|Figure 2: MRI Brain showing CSF intensity cystic lesion lined with white matter in right frontal region communicating with frontal horn of right ventricle, apprearing hyperintense on T2WI and hypointense on T1WI and FLAIR sequences – suggestive of Porencephalic|
Click here to view
It is usually diagnosed in infancy. Infants with porencephaly may exhibit hemiparesis or hemiplegia contralateral to the lesion with developmental delay., Other complications include distal hypertonicity, spasticity and truncal ataxia.13 Rarely, a porencephalic cyst may or present with CSF rhinorrhea or otorrhea., They may have poor or absent speech development, epilepsy, hydrocephalus, spastic contracture and cognitive impairment. Occasionally children with porencephaly have normal neurological development but no specific data is available.
The differential diagnosis of porencephaly includes schizencephaly, arachnoid cysts, cystic neoplasms and hydrocephalus. In schizencephaly, there are clefts with smooth contours while in porencephaly, cavities are round with a jagged contour and may contain blood clots or debris. Fetal MRI may be helpful in the third trimester to see if defect is lined with white matter (porencephaly) or gray matter (schizencephaly). Arachnoid cysts are usually smooth-walled, asymmetrical and do not communicate with the lateral ventricles. They also have a mass effect which is not seen in porencephaly. Cystic neoplasms are rare and they also have a mass effect with both solid and cystic components. Hydrocephalus can be easily distinguished from porencephaly by noting the distinguishing features of hydrocephalus.
The prognosis of porencephaly depends on the location and extent of the cyst. In some patients it presents as minor neurological problems without affecting intelligence, our patient presented with associated myaesthenia which has not been reported previously. It may also present with serious life- threatening disabilities leading to death even before the second decade.
At present no specific treatment is available. The various treatment options used are removing the cysts surgically, antiepileptics, placing a shunt, rehabilitation and physical therapies. Lifelong treatment and monitoring is necessary for the most severe cases.
COL4A1 has been proved to be a major locus for genetic predisposition to perinatal cerebral haemorrhage and porencephaly. Many other diseases have also been proved to be associated with COL4A1 mutations. These disorders cover a spectrum of overlapping phenotypes characterized by a small-vessel brain disease of varying severity including porencephaly, variably associated with eye defects (congenital cataract, retinal arterial tortuosity, eye anterior segment anomaly of Axenfeld-Rieger type) and systemic findings (muscle cramps and/or serum creatine kinase (CK) elevation, kidney involvement, cerebral aneurysms, Raynaud phenomenon, cardiac arrhythmia, and hemolytic anemia).,,,
The COL4A1-related disorders are inherited in an autosomal dominant manner. Thus, most individuals diagnosed with a COL4A1-related disorder have an affected parent. However the family history in some may be negative. The proportion of cases caused by a de novo pathogenic variant is estimated to be at least 27%. This is supposed to be because of failure to recognize the disorder in family members, early death of the parent before onset of symptoms, or late onset of the disease in the affected parent. Therefore, an apparently negative family history should be confirmed with molecular genetic testing of the parents.
The diagnosis of a COL4A1-related disorder is established in a patient with suggestive features and the identification of a heterozygous pathogenic variant in COL4A1. Once the COL4A1 pathogenic variant has been identified in an affected family member, prenatal testing and pre implantation genetic diagnosis for a pregnancy at increased risk for a COL4A1-related disorder may be done.
Genetic counselling can lower the risk of recurrence in familial cases. The optimal time for determination of genetic risk and discussion of the availability of prenatal testing is before pregnancy. Cesarean delivery is recommended for pregnancies in which the fetus is at risk for a COL4A1-related disorder to prevent brain vascular injury.
Conclusion: Porencephaly is at present a rare genetic disorder which has been lately proved to be associated with COL4A1 mutation which has autosomal dominant inheritance and can manifest as many entities other than porencephaly. Thus, although rare at present, its incidence may increase in future. The best way to contain the increase in incidence of porencephaly is genetic counselling and prenatal testing in affected individuals and those at risk. This will also help in restricting increase in other disorders related to COL4A1 mutation.
| References|| |
LeCount ER, Semerak CB. Porencephaly. Archives of Neurology & Psychiatry. 1925 Sep 1;14(3):365-83.
NAEF RW. Clinical features of porencephaly: a review of thirty-two cases. AMA Archives of Neurology & Psychiatry. 1958 Aug 1;80(2):133- 47.
Resende M, Abrunhosa J, Gonçalves P, Dos Santos JG, Moreira F, Dos Santos AG. Traumatic porencephalic cyst and cholesteatoma of the ear. Journal of Laryngology & Otology. 2000 Nov 1;114(11):864-6.
Ho SS, Kuzniecky RI, Gilliam F, Faught E, Bebin M, Morawetz R. Congenital porencephaly: MR features and relationship to hippocampal sclerosis. American journal of neuroradiology. 1998 Jan 1;19(1):135-41.
Stevenson RE, Hall JG. Porencephaly. Human Malformations and related Anomalies. Oxford University Press. 2006;2:645-54.
Volpe JJ. Neurology of the newborn. 3.Ed. Philadelphia: Saunders, 1995.
Weidenheim KM, Bodhireddy SR, Nuovo GJ, Nelson SJ, Dickson DW. Multicystic encephalopathy: review of eight cases with etiologic considerations. Journal of Neuropathology & Experimental Neurology. 1995 Mar 1;54(2):268-75.
Ferrer I, Navarro C. Multicystic encephalomalacia of infancy: clinico- pathological report of 7 cases. Journal of the neurological sciences. 1978 Sep 1;38(2):179-89.
Kotlarek F, Rodewig R, Brüll D, Zeumer H. Computed tomographic findings in congenital hemiparesis in childhood and their relation to etiology and prognosis. Neuropediatrics. 1981 May;12(02):101-9.
Erasmus C, Blackwood W, Wilson J. Infantile multicystic encephalomalacia after maternal bee sting anaphylaxis during pregnancy. Archives of disease in childhood. 1982 Oct 1;57(10):785-7.
Wiklund LM, Uvebrant P, Flodmark O. Morphology of cerebral lesions in children with congenital hemiplegia. Neuroradiology. 1990 May 1;32(3):179-86.
Barkovich AJ. Pediatric neuroimaging. 3.Ed. Lippincott Williams and Wilkins, 2000.
Eller KM, Kuller JA. Fetal porencephaly: a review of etiology, diagnosis, and prognosis. Obstetrical & gynecological survey. 1995 Sep 1;50(9):684-7.
Pasternak JF, Mantovani JF, Volpe JJ. Porencephaly from periventricular intracerebral hemorrhage in a premature infant. American Journal of Diseases of Children. 1980 Jul 1;134(7):673-5.
Jenkins HA, Konrad HR, Dodson TR. Porencephalic cyst of the mastoid. Archives of Otolaryngology. 1976 Sep 1;102(9):563-5.
Tokoro K, Fujii S, Kubota A, Yamamoto I, Maegawa J, Saijo M, Yoshida T. Successful closure of recurrent traumatic CSF rhinorrhea using the free rectus abdominis muscle flap. Surgical neurology. 2000 Mar 31;53(3):275-80.
Pilu G, Malinger G, Buyukkurt S: Porencephaly. Visual Encyclopedia of Ultrasound in Obstetrics and Gynecology, www.isuog.org
, (July 2011).
Breedveld G, De Coo IF, Lequin MH, Arts WF, Heutink P, Gould DB, John SW, Oostra B, Mancini GM. Novel mutations in three families confirm a major role of COL4A1 in hereditary porencephaly. Journal of medical genetics. 2006 Jun 1;43(6):490-5.
Coupry I, Sibon I, Mortemousque B, Rouanet F, Mine M, Goizet C. Ophthalmological features associated with COL4A1 mutations. Archives of Ophthalmology. 2010 Apr 1;128(4):483-9.
Ophoff RA, DeYoung J, Service SK, Joosse M, Caffo NA, Sandkuijl LA, Terwindt GM, Haan J, van den Maagdenberg AM, Jen J, Baloh RW. Hereditary vascular retinopathy, cerebroretinal vasculopathy, and hereditary endotheliopathy with retinopathy, nephropathy, and stroke map to a single locus on chromosome 3p21. 1-p21. 3. The American Journal of Human Genetics. 2001 Aug 31;69(2):447-53.
Gould DB, Phalan FC, Breedveld GJ, van Mil SE, Smith RS, Schimenti JC, Aguglia U, van der Knaap MS, Heutink P, John SW. Mutations in Col4a1 cause perinatal cerebral hemorrhage and porencephaly. Science. 2005 May 20;308(5725):1167-71.
Gould DB, Phalan FC, van Mil SE, Sundberg JP, Vahedi K, Massin P, Bousser MG, Heutink P, Miner JH, Tournier-Lasserve E, John SW. Role of COL4A1 in small-vessel disease and hemorrhagic stroke. New England Journal of Medicine. 2006 Apr 6;354(14):1489-96.
Meuwissen ME, Halley DJ, Smit LS, Lequin MH, Cobben JM, de Coo R, van Harssel J, Sallevelt S, Woldringh G, van der Knaap MS, de Vries LS. The expanding phenotype of COL4A1 and COL4A2 mutations: clinical data on 13 newly identified families and a review of the literature. Genetics in Medicine. 2015 Feb 26;17(11):843-53.
[Figure 1], [Figure 2]