Absent Limb Research Articles

Stroke as the initial manifestation of Takayasu’s arteritis: a Case report

Takayasu’s arteritis is a chronic inflammatory and stenotic disease of medium and large sized arteries. We report clinical, laboratory and imaging findings of a 23 year old girl who presented with history of sudden onset of left hemiparesis, absent bilateral upper limb and right carotid pulsations, an elevated ESR of 58 mm at 1 hour,C-reactive protein level of 34.9 mg/L.Imaging studies showed non hemorrhagic acute infarct in territory of right MCA, concentric wall thickening and resultant stenosis of most of the branches of aortic arch. The diagnosis of Takayasu’s arteritis was made and was put on steroids and anticoagulants. Patient showed a good clinical response.

Mutations in α- and β-tubulin encoding genes: implications in brain malformations.

The tubulin gene family is mainly expressed in post-mitotic neurons during cortical development with a specific spatial and temporal expression pattern. Members of this family encode dimeric proteins consisting of two closely related subunits (α and β), representing the major constituents of microtubules. Tubulin genes play a crucial role in the mechanisms of the Central Nervous System development such as neuronal migration and axonal guidance (axon outgrowth and maintenance). Different mutations in α/β-tubulin genes (TUBA1A, TUBA8, TUBB2A, TUBB4A, TUBB2B, TUBB3, and TUBB) might alter the dynamic properties and functions of microtubules in several ways, effecting a reduction in the number of functional tubulin heterodimers and causing alterations in GTP binding and disruptions of the binding of other proteins to microtubules (motor proteins and other microtubule interacting proteins). In recent years an increasing number of brain malformations has been associated with mutations in tubulin genes: malformations of cortical development such as lissencephaly and various grades of gyral disorganization, focal or diffuse polymicrogyria and open or closed-lips schizencephaly as likely consequences of an altered neuronal migration process; abnormalities or agenesis of the midline commissural structures (anterior commissure, corpus callosum and fornix), hypoplasia of the oculomotor and optic nerves, dysmorphisms of the hind-brain as expression of axon guidance disorders. Dysmorphisms of the basal ganglia (fusion between the caudate nucleus and putamen with absence of the anterior limb of the internal capsule) and hippocampi were also observed. A rare form of leukoencephalopathy characterized by hypomyelination with atrophy of the basal ganglia an cerebellum (H-ABC) was also recently described. The present review, describing the structural and functional features of tubulin genes, aims to revise the main cerebral associated malformations and related clinical aspects, suggesting a genotype-phenotype correlation.

Assessment of Strength & Velocity Parameters of Hip Joint Muscles in Rehabilitation of a Patient with Lower Limb Amelia. Case Study

We studied a 19-year-old patient with congenital partial absence of certain left lower limb structures (amelia) with no additional developmental defects. The patient had no fibula or foot bones and the tibia was reduced to 3 cm, which made it impossible to use a crural prosthesis. The aim of the study was to assess the strength capacity of muscles influencing the ipsi- and contralateral hip joint in the amelic patient. Compared to healthy individuals, patients with a congenital absence of lower limb demonstrate a marked disproportion in muscle peak torque between hip flexors and hip extensors, which may lead to damage to the weaker muscle group. The disproportions may be reduced with a rehabilitation programme aimed to strengthen the hip joint extensors.

Activation of the human mirror neuron system during the observation of the manipulation of virtual tools in the absence of a visible effector limb

This work explores the mirror neuron system activity produced by the observation of virtual tool manipulations in the absence of a visible effector limb. Functional MRI data was obtained from healthy right-handed participants who manipulated a virtual paddle in the context of a digital game and watched replays of their actions. The results show how action observation produced extended bilateral activations in the parietofrontal mirror neuron system. At the same time, three regions in the left hemisphere (in the primary motor and the primary somatosensory cortex, the supplementary motor area and the dorsolateral prefrontal cortex) showed a reduced BOLD, possibly related with the prevention of inappropriate motor execution. These results can be of interest for researchers and developers working in the field of action observation neurorehabilitation.

Coexistence of Charcot‐Marie‐Tooth disease type 1A and anti‐MAG neuropathy

At age 35, a man with a genetic diagnosis of Charcot-Marie-Tooth disease type 1A (CMT1A) but no family history of neuropathy and no clinical symptoms developed rapidly progressive loss of balance, distal limb numbness, loss of manual dexterity, and hand tremor. Five years later, he walked with support and had mild pes cavus, marked sensory ataxia, severe leg and hand weakness, absent deep tendon reflexes (DTRs), severe sensory loss, and hand tremor. He had dramatically reduced motor nerve conduction velocity (MNCV), strikingly prolonged motor distal latencies, absent sensory action potentials and lower limb compound muscle action potentials. CMT1A duplication was reconfirmed but the dramatic change in his clinical course suggested a superimposed acquired neuropathy. An IgM-kappa monoclonal gammopathy of uncertain significance (MGUS) with high titer anti-myelin associated glycoprotein (anti-MAG) activity was found. Nerve biopsy showed severe loss of myelinated fibers with onion bulbs, no evidence of uncompacted myelin, and few IgM deposits. Rituximab was given and he improved. It is very likely that this is a chance association of two rare and slowly progressive neuropathies; rapidly worsening course may have been due to a "double hit". Interestingly, there are reports of possible superimposition of dysimmune neuropathies on hereditary ones, and the influence of the immune system on inherited neuropathies is matter for debate.

Ectopic Limb in the Left Side of the Thorax

We report a case of ectopic left upper limb located in the left side of the thorax in a 3-day neonate. The patient had dyspnea and deficiency of the left upper limb. Multidetector computed tomography (Fig 1A,B, arrow) revealed an “armlike” structure occupying most of the left side of the thoracic cavity; it included the humerus, ulna, radius, and palm. The bony structure was folded, with a mixed-intensity mass around it, consisting of muscle and fat (Fig 1C, arrow). It was firmly adherent to the left border of the mediastinum, leading to left pulmonary atelectasis and displacement of the heart. The lesion was removed by a radical surgical procedure. Congenital upper limb defects are extremely rare, with an incidence of 0.4%, and may be accompanied by other anomalies or syndromes [1] .A n absent limb located in the thorax has been especially rare; we have not been able to trace other similar records in the literature. In our case, the images offered detailed information to enable the patient to be scheduled for operation.

Motor and parietal cortex stimulation for phantom limb pain and sensations

Limb amputation may lead to chronic painful sensations referred to the absent limb, ie phantom limb pain (PLP), which is likely subtended by maladaptive plasticity. The present study investigated whether transcranial direct current stimulation (tDCS), a noninvasive technique of brain stimulation that can modulate neuroplasticity, can reduce PLP. In 2 double-blind, sham-controlled experiments in subjects with unilateral lower or upper limb amputation, we measured the effects of a single session of tDCS (2mA, 15min) of the primary motor cortex (M1) and of the posterior parietal cortex (PPC) on PLP, stump pain, nonpainful phantom limb sensations and telescoping. Anodal tDCS of M1 induced a selective short-lasting decrease of PLP, whereas cathodal tDCS of PPC induced a selective short-lasting decrease of nonpainful phantom sensations; stump pain and telescoping were not affected by parietal or by motor tDCS. These findings demonstrate that painful and nonpainful phantom limb sensations are dissociable phenomena. PLP is associated primarily with cortical excitability shifts in the sensorimotor network; increasing excitability in this system by anodal tDCS has an antalgic effect on PLP. Conversely, nonpainful phantom sensations are associated to a hyperexcitation of PPC that can be normalized by cathodal tDCS. This evidence highlights the relationship between the level of excitability of different cortical areas, which underpins maladaptive plasticity following limb amputation and the phenomenology of phantom limb, and it opens up new opportunities for the use of tDCS in the treatment of PLP.

The Limb-Abdominal Wall Complex Defects, a form of Amniotic Band Sydrome: A Rare Case Report.

The limb-body wall complex defects a form of amniotic band syndrome which consists of a polymal formation with a thoracic and /or an abdominal-schisis, eventration of the internal organ and anomalies of the extremities. We are presenting a case of a limb-body wall complex defect with the phenotype of a placenta-abdominal attachment, anomalies of the abdominal wall defect, absence of the right lower limb and genitourinary defects.

Radicular Pain from Lumbar Canal Stenosis in Addition to Pre-Existing Phantom Limb Pain

Phantom limb (PL) is a term used to designate the sensation of the presence of an extremity following amputation, and it may be seen immediately after injury or years later in the part of the body that is deafferented or amputated. Phantom limb pain (PLP) is the term used to describe painful sensations referred to the absent limb. We present a case of a 71-year-old male with spinal claudication from discoligamentous lumbar canal stenosis L3-L4 and L4-L5 with L5 radicular pain in the left PL 13 years after the amputation. The patient had a disappearance of his radicular pain in the left PL following microsurgical lumbar decompression of L3-L4 and L4-L5. This is one of the rare cases reported in the literature in which a radicular pain in the PL disappeared following surgical decompression of the spinal canal.

Omphalocele major with absent lower limb.

A newborn delivered by Caesarian section presented with an absent anterior abdominal wall and visible bowel loops and liver. The defect was covered by a thin membrane. The patient had associated absent left lower limb and right foot fusion defect. The patient was haemodynamically stable; general condition was average. No genito-urinary abnormality was detected. The anal opening was present normally, and the patient passed meconium immediately after birth. A diagnosis of omphalocele major with amelia was made. The patient was initially managed by topical application of povidone-iodine for eschar formation and epithelisation of the sac. The patient was discharged after 1week with advice for regular follow-up.

Takayasu’s Arteritis and Mitral Stenosis

A young female presented with NYHA class III symptoms, absent lower limb and left radial pulses.Echocardiography showed severe mitral stenosis and left atrial clot. Abdominal aorta was cut off distal to renal artery with collaterals to lower limb vessels. Left subclavian artery was totally occluded distal to vertebral artery. She had HLA DR3.

Peripheral Arterial Disease Masquerading as Low Back Pain

A 49-yr old man was referred by primary care for evaluation of low back pain. The patient reported chronic mild axial lumbar region pain with a more recent onset of left gluteal/hip and thigh region pain, with the latter being more bothersome. This newer pain was described as a “fatigue” sensation that only occurred after walking for approximately 15 mins and promptly resolved with rest. He denied any radiation of this pain to the distal lower limb or any lower limb neurologic symptoms. His medical history was significant for hypercholesterolemia, hypertension, and a 70–pack year smoking history. Lumbar examination was benign, with no tenderness and full pain-free range of motion. Lower limb neurologic examination result was normal as well. Vascular examination was notable for an absent left pedal pulse and reproduction of the patient’s typical left gluteal/hip region symptoms after ambulating 10 mins. Lumbar radiographs demonstrated degenerative disc changes at L4–5 and L5–S1. The patient was referred for Ankle-Brachial Index measurements. Results revealed moderately severe left peripheral arterial disease (Ankle-Brachial Index: left, 0.62; right, 0.91). Vascular surgery was consulted and a computed tomography angiogram (Fig. 1) demonstrated occlusion of the entire left external iliac artery. One month later, the patient underwent left ileofemoral bypass, which resulted in the complete resolution of his left gluteal/hip region claudication symptoms. Follow-up Ankle-Brachial Index measurement 3 days after surgery showed marked improvement (left, 1.02; right, 1.10).FIGURE 1: Computed tomography angiogram demonstrating a long segment occlusion of the left external iliac artery.Low back pain remains one of the most common reasons for physician visits in the United States.1 A single specific etiologic diagnosis is infrequently identified in most low back pain patients.2 Although the differential for low back pain is quite broad, physicians must remain cognizant of less common but treatable causes of regional low back pain. This case highlights the importance of paying close attention to the salient aspects of a patient’s history. In this patient with multiple cardiovascular risk factors, the recent onset of new proximal limb symptoms was exacerbated by exertion and was alleviated with rest, and an absent lower limb pulse on examination all pointed to vascular claudication as the etiology for his pain. Peripheral arterial disease typically presents with posterior distal leg pain. However, this patient’s symptoms were more consistent with proximal vessel peripheral arterial disease, and this suspicion was confirmed with the Ankle-Brachial Index measurement and computed tomography angiogram. Complete and successful resolution of his symptoms with a vascular bypass procedure further confirmed this diagnosis.

A teenager with uncontrolled hypertension: a case report

BackgroundTakayasu Arteritis is a vasculitis occurring mostly in young females which may present in diverse ways. Here we report a teenager with Takayasu Arteritis who presented with uncontrolled hypertension. This case depicts an atypical presentation of this disease where the girl visited many physicians for controlling the level of hypertension and put a diagnostic dilemma about the underlying etiology of young hypertension.Case presentationA 13 year old girl presented with epistaxis, persistent headache and uncontrolled hypertension. Her clinical examination revealed normal radial, very feeble femoral and absent other lower limb pulses. There was a blood pressure discrepancy of 50/40 mm of Hg between two arms. There were bruits over multiple areas including the abdominal aorta. She had features of left ventricular hypertrophy. Her Arch aortogram showed hugely dilated arch of aorta which became abruptly normal just after origin of left subclavian artery. There was ostio-proximal stenosis of right bracheocephalic artery, left common carotid and left subclavian artery with post stenotic dilatation of all the vessels. Abdominal aortogram revealed critical stenosis of abdominal aorta above the origin of renal arteries with a pressure gradient of 80/11 mm of Hg.ConclusionTakayasu’s Arteritis should also be kept in mind while searching for the cause of uncontrolled hypertension in the young age group.

Novel Bone Marrow Failure Syndrome Due to a Deletion of the EVI1/Mecom Gene.

AbstractAbstract 2368We report on a patient born with severe congenital abnormalities including macrocephaly, brain MRI abnormalities, bilateral clubfeet, and bone marrow failure with pancytopenia presenting with none but T-lymphocytes in the peripheral blood.A 824 kb to 868 kb heterozygous deletion on chromosome 3q26.2 was identified by array-CGH on peripheral blood using an Agilent 180k oligo array (Amadid 023363). The deletion truncated the 3' part of EVI1/MECOM and extended into microRNA 551b (MIR551B). The 3' MECOM deletion was confirmed by FISH using a MECOM specific probe on uncultured peripheral blood cells in 10 investigated metaphases and 200 interphase nuclei. To assess whether the deletion was constitutional, FISH analysis was performed on buccal swaps and cultured skin fibroblasts. Loss of one MECOM signal was observed in 200 interphases, and 10 metaphases of cells derived from buccal mucosa and skin fibroblasts, respectively, demonstrating the constitutional nature of the 3' MECOM deletion. Karyotyping and FISH analysis of both parents did not reveal a structural or numerical abnormality of 3q26.2 MECOM, indicating the deletion to be de novo.EVI1/MECOM is a transcriptional regulator essential for maintaining embryonic and adult hematopoietic stem cells by directly regulating transcription of GATA2. In mouse models, homozygous disruption of MECOM results in embryonic lethality, with hypocellular bone marrow, reduced body size, small or absent limb buds, abnormal development of the nervous system and heart and massive hemorrhaging. Furthermore, MECOM heterozygosity leads to a marked impairment of the self-renewal capacity of hematopoietic stem cells.In our case the heterozygous deletion results in 3' terminal truncated MECOM lacking the C-terminal acidic amino acid cluster domain (AD) encoding sequences. The AD of MECOM is important for activation of GATA2 transcription in vitro. This supports the notion that haploinsufficiency of MECOM causes bone marrow failure due to loss of critical MECOM transcriptional AD encoding sequences in this case, supposedly by deregulating GATA2 mediated control of hematopoietic stem cell homeostasis.We will discuss our data in relation to one seemingly similar case deposited recently in the DECIPHER database. In conclusion, we report on a novel 3q26 EVI1/MECOM deletion syndrome with multiple severe congenital abnormalities and bone marrow failure due to EVI1/MECOM haploinsufficiency. Disclosures:No relevant conflicts of interest to declare.

D.P.11 Dual pathology identified by next generation sequencing in siblings with peripheral neuropathy, ataxia and retinal dystrophy

Two children, born to healthy consanguineous South Asian parents, presented with recurrent aspiration in infancy, peripheral neuropathy, ataxia and retinal dystrophy. The older child had pyrexias and pneumonia in infancy due to aspiration, requiring gastrostomy and fundoplication. Nystagmus was noted aged 8months with subsequent visual impairment and signs of rod-cone retinal dystrophy on ERG. By 18months she had severe motor delay, generalised hypotonia and absent lower limb reflexes. EMG and NCVs indicated a severe demyelinating neuropathy. By 5years she was markedly ataxic and had developed a progressive scoliosis. Cranial MRI demonstrated delayed myelination but no cerebellar abnormalities. No mutations were identified in the PMP22, MPZ or GDAP1 genes and transferrin IEF, ATM, aprataxin, senataxin and vitamin E levels were normal. Muscle biopsy showed some reduction of activity of respiratory chain complexes 4 and 5 but no underlying mitochondrial abnormality was identified. The younger sibling had a similar presentation but had silent aspiration which did not require surgery and had no scoliosis at age 7. Autozygosity mapping identified seven regions of autozygosity >2Mb, on chromosomes 5, 8, 11, 12(x2), 13 and 22. Using exome capture Agent SureSelect all exon kit on an ABI SOLiD 4.0 platform, seven homozygous variants were identified within these regions. One was a c.627T>G; p.Phe209Leu mutation in the PDE6A gene, known to cause Retinitis Pigmentosa 43. Another was a novel c.1585C>T; p.Arg529Cys variant in the SH3TC2 gene, which is associated with CMT type 4C. Both mutations were confirmed by Sanger sequencing. These genes are separated by only 800kb and are therefore unlikely to segregate independently. Attempts at reaching a clinical diagnosis in these siblings had been directed towards identifying a single underlying disorder. The molecular findings indicated that they had dual pathology, illustrating the diagnostic power of new genetic technologies.

Skeletal development in the fossorial gymnophthalmids Calyptommatus sinebrachiatus and Nothobachia ablephara

The development of the cartilaginous and bony elements that form the skull and axial and appendicular skeleton is described in detail for the post-ovipositional embryonic development of the fossorial gymnophthalmid species Calyptommatus sinebrachiatus and Nothobachia ablephara. Both species have a snake-like morphology, showing an elongated body and reduced or absent limbs, as well as modifications in skull bones for burrowing, such as complex articulation surfaces and development of bony extensions that enclose and protect the brain. Similar morphological changes have originated independently in several squamate groups, including the one that led to the snake radiation. This study characterizes the patterns of chondrogenesis and osteogenesis, with special emphasis on the features associated with the burrowing habit, and may be used for future comparative analyses of the developmental patterns involved in the origin of the convergent serpentiform morphologies.

MiR-886-3p Levels Are Elevated in Friedreich Ataxia

Friedreich ataxia (FRDA) is the most common inherited ataxia caused primarily by an intronic GAA.TTC triplet repeat expansion in the frataxin (FXN) gene. FXN RNA and protein levels are reduced in patients leading to progressive gait and limb ataxia, sensory loss, reduced tendon reflexes, dysarthria, absent lower limb reflexes, and loss of position and vibration sense. Neurological manifestations ensue from primary loss of dorsal root ganglia neurons and their associated axons ascending centrally in the spinal cord and peripherally in large myelinated nerves. Small noncoding RNAs such as microRNAs have been shown to be dysregulated in neurodegenerative diseases such as Alzheimer's and Huntington's disease. Here we report that hsa-miR-886-3p (miR-886-3p) was increased in patient cells as well as peripheral patient blood samples. Selective reduction in miR-886-3p by an anti-miR led to elevation of FXN message and protein levels without associated changes in histone marks at the FXN locus. Nevertheless, derepression of frataxin by a histone deacetylase inhibitor leads to a decrease in miR-886-3p. These results outline involvement of a small RNA, miR-886-3p in FRDA and a novel therapeutic approach to this disease using an anti-miR-886-3p.

Clinical Features of Friedreich Ataxia

Friedreich ataxia, the most common hereditary ataxia, affects approximately 1 per 29,000 white individuals. In about 98% of these individuals, it is due to homozygosity for a GAA trinucleotide repeat expansion in intron 1 of FXN; in the other 2%, it is due to compound heterozygosity for a GAA expansion and point mutation or deletion. The condition affects multiple sites in the central and peripheral nervous system as well as a number of other organ systems, resulting in multiple signs and symptoms. Onset of this autosomal recessive condition is usually in the first 2 decades of life. Major clinical features include progressive ataxia, absent lower limb reflexes, upgoing plantar responses, and peripheral sensory neuropathy. The main nonneurological sites of morbidity are the heart, resulting in cardiomyopathy, and the pancreas, resulting in diabetes mellitus. In this review, we provide an overview of the clinical features of Friedreich ataxia and discuss differential diagnoses.

Use of Lipomodeling to Forearm Residuum to Assist Fitting of Below-Elbow Prosthesis

In Brief Congenital absence of the upper limb can be ameliorated by use of a prosthetic device. Regular prosthetic wear can be associated with skin and musculoskeletal problems. Shorter lever arm of the residual stump can cause pain over pressure points, skin ulceration, bursitis and inability to wear the prosthesis. Temporary discontinuation of prosthetic wear is used to facilitate wound dressing and healing. This inevitably leads to limitation of activity and may lead to the amputee not going to work. We describe a young patient with congenital transverse upper third forearm deficiency, who was having difficulty in wearing an upper limb prosthesis, due to the stump lacking in soft tissue cover, causing pain and poor function. This resulted in physical and emotional difficulties for the patient. The patient underwent fat graft transfer from abdomen into the limb with a successful outcome, leading to improved comfort and stability of the prosthesis. With advances in liposuction procedures and easier aspiration of fat from the body fat; fat grafting has become more widely available. Further scientific development in this field has allowed more plastic, dermatological and cosmetic surgeons to offer their patients fat transfer for functional and cosmetic benefits. However, there are no reported cases of the use of fat grafting in amputees. This case demonstrates the successful use of fat graft to improve functional outcome in an amputee. We feel fat transplants can be used in both congenital and acquired limb loss patients with similar problems with good success rates. Lipomodeling or fat grafting is a technique whereby fat is harvested from one part of the body and is transferred to another in order to correct a deficiency or relative deficiency in the subcutaneous fat layer. After a transradial amputation patient presented with recurrent pain, swelling, and blistering, and following a discussion of various treatment alternatives by the multidisciplinary team, fat grafting from the abdominal area to the tip of the residual limb was recommended. The operated site healed well, the prosthetic limb was refitted with improved comfort and stability, and the patient expressed her satisfaction with the outcome.

A review of supernumerary and absent limbs and digits of the upper limb

For years people have been enamored by anomalies of the human limbs, particularly supernumerary and absent limbs and digits. Historically, there are a number of examples of such anomalies, including royal families of ancient Chaldea, tribes from Arabia, and examples from across nineteenth century Europe. The development of the upper limbs in a growing embryo is still being elucidated with the recent advent of homeobox genes, but researchers agree that upper limbs develop between stages 12-23 through a complex embryological process. Maternal thalidomide intake during limb development is known to cause limb reduction and subsequent amelia or phocomelia. Additionally, a number of clinical reports have illustrated different limb anomaly cases, with each situation unique in phenotype and developmental abnormality. Supernumerary and absent limbs and digits are not unique to humans, and a number of animal cases have also been reported. This review of the literature illustrates the historical, anatomical, and clinical aspects of supernumerary and absent limbs and digits for the upper limb.