فهرست مطالب bahram haghi ashtiani

Amyotrophic Lateral Sclerosis (ALS) is the most common fatal motor neuron disease characterized by involvement of the combination of upper (UMNs) and lower (LMNs) motor neurons. The degeneration of LMNs and UMNs leads rapidly to progressive muscle atrophy and paralysis, dysphagia, dysarthria, fasciculations, muscle cramps, and finally death due to respiratory failure.
ALS is an adult-onset neurodegenerative disease; its age at onset (AAO) is usually 50-60 years. However, AAO of the disease is variable (1 - 94 years old). Mean survival of patients with ALS has been reported as 3-5 years from the disease onset. However, 10-20% of patients survive more than 10 years. The incidence and prevalence of ALS in the European population is 1–2 and 2-7 people per 100,000, respectively.
Due to the great clinical variability in ALS manifestations, the diagnosis of ALS can be challenging. Thus, the El Escorial criteria were developed based on clinical data to ALS diagnosis.
ALS can be categorized into different forms:

It can be classified into familial and sporadic based on the presence and absence of other patients in the family. Most ALS cases are sporadic (SALS) and only about 1-13% of ALS cases are familial (FALS).
It can be sub-grouped based on the mode of inheritance of the disease; autosomal dominant, autosomal recessive, X-linked, mitochondrial or de novo.
ALS can be categorized based on the age at onset of the disease: juvenile ALS; age at onset below 25 years, and adult ALS; the onset age is over 25 years old - usually the onset age of the disease is over 45 years old.
ALS can be classified based on the locus and gene involved in the development of the disease. To date, more than 40 ALS-causative genes have been identified. These loci are only responsible for about two-thirds of FALS and about 10% of SALS.


Molecular analyses of the known ALS genes have demonstrated that their encoded proteins are involved in several physiological pathways, including, oxidative stress, axonal transport, autophagy, proteins folding, glutamate excitotoxicity, RNA metabolism and involvement of non-neuronal cells (microglia, astrocytes and oligodendrocytes).
Among the ALS-causative known genes, five genes including SOD1, C9orf72, TARDBP, FUS/TLS and TBK1 seem to more important and account for about 15% of all ALS patients. Meanwhile, mutations of SOD1 and C9orf72 genes are detected in a significant percent of patients.
Superoxide dismutase 1 gene - SOD1 - is the first gene identified for ALS disease. Mutations of this gene have been observed in 20% (12-23%) of FALS cases and about 3% (1-7%) of SALS patients.
The repetitive sequence of six nucleotides (GGGGCC; G4C2)n in intron 1 of the C9orf72 gene was also associated with ALS. The number of G4C2 repeats in healthy people is less than 23, while in affected individuals, the number of these repetitions was more than 23 and up to 1500 and even more. The dynamics of such repetitions in this gene may be an explanation for the phenotypic variability and different penetrance of the disease in these families.
The cause of most ALS cases is not yet known, but it is certain that several cellular functions are disturbed in the motor neurons of these patients, which can probably lead to the degeneration of these neurons. It is clear that most of the genes responsible for ALS do not exclusively play a role in the development of this disease, and mutations in these genes are not only involved in the development of ALS, but also can result in the occurrence of other neurodegenerative disorders like frontotemporal dementia (FTD), hereditary spastic paraplegia (HSP), Parkinson disease, progressive supranuclear palsy, ataxia, corticobasal syndrome, and Huntington disease-like syndrome. So, understanding the pathogenesis of ALS is essential in developing diagnostic methods and providing new effective treatments in the clinical trials.
Here, we reviewed the clinical, epidemiologic and genetic of ALS and briefly explained those in Iran. Our results showed (a) the average incidence and prevalence of ALS were 0.42/100 000, and 1.57/100 000, respectively. (b) In contrast to European countries, mutations of SOD1 are the common cause of ALS in Iranian FALS patients; they are causative in approximately 30% of the FALS cases but mutations of C9orf72 are rare. (c) A significant difference in disease progression rate is observed between patients who used riluzole and those who did not.

Myasthenia gravis (MG) is an immune-mediated potentially treatable disease in which rapid diagnosis and proper treatment can control symptoms. Treatment should be individualized in each patient according to distribution (ocular or generalized) and severity of the weakness, antibody status, thymus pathology, patient comorbidities, and preferences. A group of Iranian neuromuscular specialists have written these recommendations to treat MG based on national conditions. Four of the authors performed an extensive literature review, including PubMed, EMBASE, and Google Scholar, from 1932 to 2020 before the central meeting to define headings and subheadings. The experts held a 2-day session where the primary drafts were discussed point by point. Primary algorithms for the management of MG patients were prepared in the panel discussion. After the panel, the discussions continued in virtual group discussions, and the prepared guideline was finalized after agreement and concordance between the panel members. Finally, a total of 71 expert recommendations were included. We attempted to develop a guideline based on Iran’s local requirements. We hope that these guidelines help healthcare professionals in proper treatment and follow-up of patients with MG.

Carpal tunnel syndrome (CTS) is the most prevalent entrapment syndrome in the upper limbs, for which pregnancy is a known risk factor. CTS diagnosis is confirmed via nerve conduction studies (NCSs), which sometimes is expensive, and the electrical stimulation makes it an unpleasant diagnostic modality, especially for pregnant subjects. Recently, high-frequency ultrasonography (HF-USG) is known as a diagnostic method. This study is concerned with determining the diagnostic value of this modality for CTS among pregnant women.

This cross-sectional case-control study was conducted with 40 CTS cases and 40 matched controls. The HF-USG of wrists was performed bilaterally on all participants with a focus on the median nerve cross-sectional area (MNCSA) at the carpal tunnel (CT) inlet.

Mean MNCSA was statistically different between the CTS group (11.71 ± 1.86 mm2, range: 8 to 18 mm2) and the control group (6.75 ± 1.38 mm2, range: 4 to 11 mm2) (P < 0.001). The receiver operating characteristic (ROC) curve was drawn, and the cross-sectional area (CSA) cut-off point of 8.5 mm2 showed sensitivity and specificity of 98% and 93%, respectively. The positive predictive value (PPV) and the negative predictive value (NPV) were 95% and 98%, respectively, with the mentioned point as the diagnostic threshold.

HF-USG of the median nerve can be utilized as a preferable alternative to NCS (the current gold standard diagnostic method) in pregnant women, due to its convenience and lower cost, or at least, it can be used as a screening tool among pregnant women with suspicious symptoms.

Amyotrophic Lateral Sclerosis-Specific Quality of Life-Revised (ALSSQOL-R) encompasses 50 items which assess quality of life (QOL) in patients with amyotrophic lateral sclerosis (ALS) in six major domains. This study aims to translate the ALSSQOL-R into Persian and evaluate its reliability and validity among Iranian patients.

ALSSQOL-R was translated by the standard multi-step forward-backward method. Content validity was calculated using item content validity index (I-CVI). Three items in the “intimacy” domain were deleted considering Iranian culture. Cronbach’s alpha was used for all 6 dimensions to calculate the internal consistency reliability. Test-retest reliability was evaluated using intraclass correlation coefficient (ICC) with one-month interval. Concurrent validity was measured by the validated version of 36-Item Short Form Health Survey (SF-36) questionnaire.

Sixty-three patients with ALS were enrolled in the study. I-CVI was 70%, promoted to 85% after modifications (acceptable). Regarding internal consistency reliability, Cronbach’s alpha in all six domains was ³ 0.70 and total Cronbach’s alpha was 0.89 which is assumed as good. In terms of test-retest reliability, ICC [95% confidence interval (CI)] was 0.91 (91%) and Pearson correlation coefficient (r) was 0.90 (P < 0.001), all indicating an excellent reliability. The concurrent validity was established based on a strong correlation with SF-36 (r = 0.744, P < 0.001).

The findings show that the modified Persian version of ALSSQOL-R is a valid and reliable QOL questionnaire which can be used for Iranian patients with ALS in both clinical and research settings.

Post traumatic lumbosacral plexopathy (LSP) is a well-known condition following pelvic fracture or abdominal trauma and surgery. A rare condition of LSP has been reported in the literature following femoral shaft fractures.  

Two cases of LSP after bilateral femoral shaft fracture presented to our center. In both cases, the mechanism of injury was a high energy trauma without any signs or symptoms of pelvic or spinal injury. Electrodiagnostic studies confirmed acute plexopathy and spontaneous recovery occurred in both.  

LSP can be seen in association with fractures or traumas far from anatomical location of the plexus. Multidisciplinary approach and complete accurate examination are mandatory for diagnosis management of the condition.

Few studies have reported the association of Guillain-Barre syndrome (GBS) and coronavirus disease-2019 (COVID-19) infection. In this study, we reported GBS in six patients infected with COVID-19 and reviewed all existing literature about GBS in association with COVID-19.

This study was performed in three referral centers of COVID-19 in Iran, and six patients with the diagnosis of GBS were enrolled. Patients enrolled in the study with acute progressive weakness according to the demyelinating or axonal variant of GBS, according to Uncini's criteria.

Four of our patients had axonal polyneuropathy, two patients had demyelinating polyneuropathy, and one patient required mechanical ventilation. All our patients had a favorable response to treatment. In one patient, the GBS symptoms recurred four months after the first episode.

Limited case reports suggest a possible association between GBS and COVID-19. Such associations may be an incidental concurrence or a real cause-and-effect linkage; however, more patients with epidemiological studies are necessary to support a causal relationship.

The new coronavirus virus 2019 (COVID-19) has affected many routine medical activities, including medical education and clinical activities. The social isolation has led to highlighting virtual learning and telemedicine. We present a report of our adoptive procedures taken during the outbreak of COVID-19 in our tertiary healthcare center and compare the current educational and clinical issues with these issues one month before the outbreak. Virtual learning is a useful replacement in this critical situation.

We aimed to compare the sonographic measurement of median nerve cross-section area (CSA) in patients with Amyotrophic Lateral Sclerosis (ALS) and healthy individuals. The effect of duration of the disease on correlations between paraclinical findings and ALS functional rating scale (ALSFRS) were secondarily aimed to be evaluated. The cross-sectional study was approved by the Ethical Committee of Iran University of Medical Sciences and conducted between January 2017 and December 2018. We evaluated the median nerve surface area by means of sonography in 35 ALS patients and 35 healthy controls. Compound muscle action potential (CMAP) amplitudes during nerve conduction study and ALSFRS were recorded by the same trained specialist. Data were analyzed using SPSS software version 18. We did not find a significant difference between CSA in ALS patients and the normal population (P>0.05). Comparing to normal individuals, the mean CMAP decreased significantly in ALS patients (6.6±3.07 mV versus 10.25±2.2 mV, P<0.001). ALSFRS correlated with both CSA of the median nerve at the wrist (P:<0.001, r:0.78) and the CMAP (P:<0.001, r:0.74) that were confirmed by regression models designed to consider the effect of disease duration on these correlations. CSA was not different between ALS patients and the normal population, but CMAP decreased in ALS patients. ALSFRS correlated with both CSA and CMAP of the median nerve.

The objective of our study was to assess Unified Parkinson Disease Rating Scale (UPDRS) score in Parkinson disease (PD) patients who underwent subthalamic nucleus (STN) deep brain stimulation (DBS) 6 years after their surgery and to compare their UPDRS score 6 years after DBS with their score before surgery and 6 months after their operation.
In this cross sectional study which was carried out at Neurology Department of Rasool-e-Akram Hospital, Tehran, Iran, affiliated to Iran University of Medical Sciences between 2008 and 2014, 37 patients with advanced PD were enrolled using non-randomized sampling method.
All of the patients underwent STN DBS surgery and one patient died before being discharged, therefore; we started our study with 36 patients. The UPDRS III total score at preoperative state, 6-month follow-up and 6-year follow-up state were compared using repeated-measure analysis of variance.
Thirty-seven patients (26 men and 10 women) with mean age of 50 ± 3 ranging from 32 to 72 years underwent STN DBS surgery. All patients were suffering from advanced PD with mean period of 11.3 ± 1.9 years. All patients except one were followed up for six months. And 14 patients (8 men and 6 women) were included in a six-year follow-up. The UPDRS score measurements before surgery, at
6-month follow-up and 6-year follow-up were
18.22 ± 2.88, 12.80 ± 3.14, 25.0 ± 11.8, respectively. Significant increase in UPDRS score was observed between the preoperative and six-year follow-up period (P In conclusion, this study suggests that total UPDRS score will increase at 5 years following STN DBS and also showed that resting tremor, one of UPDRS sub-scores, will improve over time and the benefit of DBS will be persistent even after 6 years.

Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) can involve multiple systems and cause stroke-like episodes and status epilepticus.
A 48-year-old female with history of early fatigability, migraine-type headaches, and bilateral sensory-neural hearing loss presented 3 episodes of serial seizures. On admission she was affected by Wernicke aphasia and, then, right hemiparesis. Investigations showed elevated arterial lactate and ragged red fibers on muscle biopsy.
Though more commonly diagnosed during childhood, some cases of adult-onset MELAS syndrome are reported. This syndrome should be considered in patients with stroke-like events in adults without cerebrovascular risk factors and difficult-to-treat seizures.

Meningeal melanocytoma is a rare tumor of nervous system, which originates from leptomeningeal melanocytes. The locations of melanocytoma in the nervous system are most frequently in the posterior fossa or along the spinal cord, and usually appear as an extra-axial mass. The manifestations of tumor are most often due to its compressing effect on adjacent nervous structures that causes various neurological signs and symptoms depending on its locations. It may also cause superficial siderosis of the central nervous system [1]. In this case we describe another manifestation of this tumor which raised intracranial pressure and developed its neurological signs and symptoms. The patient was a 33-year old man with a two-year history of headache and tinnitus, transient diplopia, and had also a three- month history of progressive bilateral visual and hearing loss. The medical investigations of the patient reveal raised intracranial pressure (RICP) with a high concentration of protein in the cerebrospinal fluid, and an extra-axial mass at the T11-12 level in magnetic resonance imaging of the spinal cord. The patient underwent surgical removal of the tumor, in which the pathological study characterized the tumor as a meningeal melanocytoma. After surgery the CSF pressure returned to normal state, and its protein level decreased. The patient's hearing loss improved significantly but the visual defect did not change. Base on various causes of the RICP, especially when there is abnormality in CSF protein without any known cause, we must consider melanocytoma as a treatable cause, and thus in such patients, performing spinal cord magnetic resonance imaging (MRI) is a valuble technique for diagnosis as well as investigation.