Journal scan: A review of images in clinical medicine of immediate clinical significance, harvested from major international journals

From the desk of the Editor-in-chief

Images in Clinical Medicine

1. Darier’s Sign in Solitary Mastocytoma

Haleigh Dawn Stafford, January 29, 2025, N Engl J Med 2025; 392:494, Vol. 392 No. 5

Abstract

A previously healthy 10-month-old girl presented with an intermittently itchy and swollen skin lesion on the neck. When rubbed, the lesion became edematous with a flare of surrounding erythema.

2. Hypothyroid Myopathy with Muscle Pseudohypertrophy

Kajananan Sivagurunathan et al, Published February 1, 2025, NEJM

Abstract

A 35-year-old man presented with a 2-year history of proximal muscle weakness with intermittent muscle cramping. Physical examination showed macroglossia and enlargement of the muscles in both calves.

A 35-year-old man presented to the medical ward with a 2-year history of progressive weakness in his arms and legs associated with intermittent muscle cramping. He also had fatigue, weight gain, and constipation. Despite his symptoms, he had been able to continue his work as a cattle herder. Vital signs were normal. On physical examination, the patient appeared fatigued. Macroglossia (Panel A) and enlargement of the muscles in both calves (Panel B) were observed, but no enlargement of muscles in the arms was seen. He had proximal muscle weakness in the arms and legs and decreased deep-tendon reflexes with delayed relaxation. Laboratory testing showed a considerably elevated thyrotropin level and low levels of free thyroxine and triiodothyronine. The creatine kinase level was 7087 U per liter (reference range, 55 to 170), and the thyroid peroxidase antibody level was markedly elevated. A diagnosis of hypothyroid myopathy with muscle pseudohypertrophy (also known as Hoffman’s syndrome) in the context of severe hypothyroidism due to Hashimoto’s thyroiditis was made.

Muscle pseudohypertrophy in hypothyroidism results from altered muscle-fiber composition and the accumulation of glycosaminoglycans in the muscle tissue.

Treatment with levothyroxine was initiated. At 3 months of follow-up, the muscle weakness had resolved, but the muscle pseudohypertrophy persisted.

3. Thyroid abscess caused by mucormycosis in a child with acute lymphoblastic leukaemia

Xu Yang et al, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(24)00753-9/abstract

A 5-year-old girl with acute lymphoblastic leukaemia (ALL) presented with inspiratory dyspnoea and fever on day 32 of chemotherapy (Chinese Children’s Cancer Group–Acute Lymphoblastic Leukemia–2020 Intermediate/High Risk protocol). This protocol was proposed in 2020 by the Chinese Children’s Cancer Group to treat children with intermediate or high risk acute lymphoblastic leukemia. On examination, a tender swelling was noted in the thyroid region of the neck. Blood examination showed low levels of leukocytes (1·7 × 109/L) and neutrophils (0·26 × 109/L). The neck ultrasonography revealed a diffusely enlarged thyroid with fluid collections and narrowing of the adjacent trachea (figure A), suggesting the presence of an abscess. MRI showed an enlarged thyroid and bilateral lesions with enhancing margins (figure B). No defect of the third or fourth brachial arch or a piriform sinus fistula was found in the examination. With ultrasound-guided aspiration, purulent discharge was extracted and subsequently sent for culture, which showed negative results. The patient was treated with intravenous meropenem for 7 days (40 mg/kg, three times daily) before we received the culture results.

Figure

  • The neck ultrasonography revealed a diffusely enlarged thyroid with fluid collections (arrows) and narrowing of the adjacent trachea (asterisk), suggesting an abscess. (B) MRI showed an enlarged thyroid and bilateral lesions with enhancing margins (arrows). (C) Haematoxylineosin stain of thyroid biopsy specimen revealed broad, aseptate, ribbon-like, and rarely-branching fungal hyphae typical for Mucorales infection (arrows). (D) The hyphae of Mucorales (arrows) were further confirmed in periodic acid-Schiff and (E) Grocott’s silver methenamine stains.

Images in Neurology

4. Ischemic Stroke Due to Compression of a Wandering Internal Carotid Artery by the Hyoid Bone

François Bouille et al, JAMA Neurol. Published online February 3, 2025. doi:10.1001/jamaneurol.2024.5028

A75-year-old man presented with sudden-onset right hemiplegia. Urgent cerebral magnetic resonance imagery (MRI) revealed an ischemic stroke in the left-middle cerebral artery territory. Thrombolysis administered 2 hours after symptom onset showed no clinical effect. Computed tomography (CT) angiography performed 3 days later revealed a 65% North American Symptomatic Carotid Endarterectomy Trial stenosis of the left internal carotid artery (ICA) due to compression by the greater horn of the hyoid bone (Figures 1A and 2). The left ICA was found to be in a retropharyngeal position. No atheromatous plaque was visible on the aortic arch, carotid arteries, or ICAs. The ICAs were not tortuous. Carotid ultrasound imagery performed the same day did not find any hemodynamic and morphological abnormalities of the left ICA.

A follow-up MRI performed 10 days after the stroke showed that the left ICA had shifted externally from the hyoid bone, relieving the compression (not shown). This suggested that the carotid artery was moving medially (wandering). Cardiac monitoring over 10 days did not reveal any abnormalities. No other cause of stroke having been found, partial hyoid bone resection was planned. A preoperative CT scan revealed a slightly renewed compression of the left ICA by the hyoid bone, without reappearance of new symptoms. Posthyoidectomy CT showed a restored appearance of the left ICA (Figure 1B).

Discussion

Several cases of stroke due to compression of the ICA by the hyoid bone have already been described in the literature.1 However, to our knowledge, this is the first case of stroke linked to compression of a wandering ICA. This poses a significant diagnostic challenge and may indicate an underappreciated cause of stroke. As our case demonstrates, the compression of a wandering ICA by the hyoid bone can be intermittent and go completely undetected on imaging examinations.

Wandering carotids2 are well known to anesthetists and surgeons, carrying various implications in clinical practice.3 Recently, Mutlu et al4 reported a case of stroke attributed to a carotid web found on a wandering ICA. To our knowledge, this is the only published case linking wandering carotid with stroke. The publication of additional cases would be necessary for a deeper comprehension of the association between wandering carotid arteries and stroke.

JAMA Neurology Clinical Challenge

5. A 61-Year-Old Man with Weakness and Gait Dysfunction

Felipe J. S. Jones etal, JAMA Neurol. Published online January 21, 2025. doi:10.1001/jamaneurol.2024.4600

Case

A61-year-old man presented with chronic progressive weakness and gait dysfunction. Four years prior, he developed progressive arm and leg weakness. He subsequently experienced recurrent falls, attributed to gait imbalance and tripping over his feet, and urinary incontinence. One year prior, his wife noted progressive memory loss (eg, getting lost when going to familiar places), dysarthria, and episodes of inappropriate laughter (ie, involuntarily laughing without a clear emotional trigger). He had a history of hypertension. There was no known history of a neurological disorder in his family. He had Ashkenazi Jewish ancestry in his maternal lineage. There was no known consanguinity. Neurological examination revealed impaired short-term recall (recalled 0 of 5 words at 5 minutes) and a pseudobulbar affect. His cranial nerve examination was notable for a spastic dysarthria without tongue fasciculations. There was upper and lower extremity spasticity, atrophy of intrinsic hand and calf muscles, and mild weakness of his intrinsic hand and distal lower extremity muscles bilaterally. There was decreased large-fiber sensation distally in his lower extremities. Romberg sign was absent. Deep tendon reflexes were 3+ at the biceps and patellars and absent at the ankles. Plantar responses were extensor bilaterally. Cerebellar function was normal. The gait was spastic. Magnetic resonance imaging (MRI) of the brain showed confluent T2/fluid-attenuated inversion recovery (FLAIR) hyperintensity in the periventricular white matter involving the corticospinal tracts, posterior limb of internal capsule, external capsule, and medial lemniscus and corticospinal tracts at the pons and medulla (Figure). MRI of the cervical and thoracic spinal cord showed diffuse atrophy without signal abnormalities. Electromyography revealed a chronic sensorimotor axonal neuropathy and lumbosacral radiculopathies. He had normal levels of vitamin B12, methylmalonic acid, copper, vitamin E, lactate/pyruvate, very long chain fatty acids, plasma/urine amino acids, and lysosomal enzymes, a normal bile acids profile, and negative infectious serologies (HIV, syphilis, and human T-lymphotropic virus). Cerebrospinal fluid analysis revealed normal cell counts, protein and glucose levels, oligoclonal band profile, and IgG index.

Magnetic resonance imaging (MRI) of the brain showing fluid-attenuated inversion recovery hyperintensity involving the periventricular regions, corticospinal tracts, posterior limb of the internal capsule, the external capsule (A) the medial lemniscus and corticospinal tracts of the medulla, cerebellar peduncle, and the dentate nuclei (B, circle).

What Is Your Diagnosis?

  • Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation.
  • LMNB1-related autosomal dominant leukodystrophy.
  • Adult polyglucosan body disease.
  • Adult-onset Alexander disease.

Diagnosis

  1. Adult polyglucosan body disease

Discussion

The presentation was suggestive of adult polyglucosan body disease (APBD), and a multigene panel revealed a compound heterozygous pathogenic missense variant in the glycogen branching enzyme 1 (GBE1) gene (c.986A>C (p.Tyr329Ser) and c.691 + 2T>C (IVS5 + 2T>C)), confirming this diagnosis.1 The Tyr329Ser variant is common in Ashkenazi Jewish patients.

APBD is a rare autosomal recessive neurodegenerative disorder, in the spectrum of glycogen storage disease type IV, caused by biallelic pathogenic GBE1 variants.1-4 The clinical presentation is heterogeneous, but the core symptoms include progressive neurogenic bladder, gait dysfunction due to mixed upper and lower motor neuron involvement (ie, myeloneuropathy), and cognitive impairment at or after age 40 years.1-4 Lower motor neuron involvement is due to a length-dependent axonal polyneuropathy and polyradiculopathies.1-4 In severe cases, an Alzheimer disease–like dementia phenotype was previously reported.1-4 The pace of progression is usually slow. In one of the largest series to date, the median age for onset of symptoms was 51 years and for wheelchair dependence and death was 63 and 70 years, respectively.4 Radiographic findings may be nonspecific and include widespread confluent and symmetric T2/FLAIR hyperintense white matter abnormalities in the periventricular regions, posterior limb of the internal capsule, and external capsule. Additional clues that (if present) suggest APBD include involvement of corticospinal tracts and medial lemniscus of the pons and medulla, superior cerebellar peduncles and dentate nuclei, and medullary and spinal cord atrophy.1-4 Although nerve biopsy may show polyglucosan bodies, definitive diagnosis is established by genetic testing via targeted GBE1 sequencing, multigene panels that include GBE1, whole-exome sequencing or whole-genome sequencing.2,3 Treatment is supportive and includes symptomatic management of spasticity, neurogenic bladder, dysautonomia, and cognitive decline.2,3

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation is caused by autosomal recessive variants in the DARS2 gene.5 Typical presentation occurs in early childhood, but adult-onset disease has been described.5 Core clinical features include slowly progressive cerebellar ataxia, lower-extremity predominant spasticity, and dorsal column dysfunction.5 Axonal neuropathy can occur. MRI reveals a distinct T2/FLAIR hyperintensity in the cerebral white matter sparing the U-fibers, involvement of posterior limbs of the internal capsule, splenium of the corpus callosum, trigeminal nerve tracts, cerebellum, and the dorsal column and lateral corticospinal tracts of the medulla and spinal cord.5 Features that allow distinction from APBD are an earlier age of onset, prominent cerebellar and sensory ataxia, and characteristic spinal cord signal abnormalities.5

LMNB-1–related autosomal dominant leukodystrophy (ADLD) presents between ages 40 to 60 years with dysautonomia followed by corticospinal tract and cerebellar dysfunction, resulting in spastic ataxia and tremors.6 MRI in ADLD can show T2/FLAIR hyperintensity predominantly in a frontoparietal distribution following the corticospinal tracts through the posterior limb of the internal capsule toward the medulla and upper and middle cerebellar peduncles.6,7 Spinal cord atrophy is common and can be associated T2/FLAIR hyperintensity in the entire cord white matter.6,7 Some distinguishing features from APBD are the different imaging pattern, sparing of the peripheral nervous system, and more prominent cerebellar dysfunction.6

Alexander disease is caused by autosomal dominant GFAP gene variants that can present across the lifespan, with adult onset occurring in approximately 33% of cases.8 The typical adult phenotype includes bulbar symptoms (eg, palatal myoclonus, dysarthria, dysphagia), cerebellar dysfunction, and corticospinal tract involvement resulting in spastic weakness.8,9 Other features include sleep disorder, dysautonomia, and parkinsonism.8 A typical MRI finding is cervicomedullary atrophy with relative pontine sparing, known as the tadpole sign.8,9 Other potential findings include cerebellar signal abnormalities, contrast-enhancing lesions, and periventricular white matter T2/FLAIR hyperintensities.8,9 Distinguishing features from APBD include sparing of the peripheral nervous system and lack of the extensive supratentorial signal abnormalities and extensive spinal cord atrophy seen in this case.8

Images in Clinical Medicine

6. Tumoral Melanosis

Deshan F. Sebaratnam, , February 12, 2025,N Engl J Med 2025;392:698,DOI: 10.1056/NEJMicm2413467,VOL. 392 NO. 7

Abstract

An 84-year-old man with a history of metastatic melanoma of the scalp who was undergoing immunotherapy presented with new, multiple blue-gray macules on the scalp

Images in Clinical Medicine

7. Pleural Paragonimiasis

Lin Wang et al, February 8, 2025,N Engl J Med 2025;392: e19,DOI: 10.1056/NEJMicm2412622,VOL. 392 NO. 7

Abstract

An asymptomatic 17-year-old boy who had emigrated from El Salvador was found to have a pleural effusion on a chest radiograph. A small number of parasite eggs were seen in the pleural fluid.

Discussion

Causal Agents

More than 30 species of trematodes (flukes) of the genus Paragonimus have been reported which infect animals and humans. Among the more than 10 species reported to infect humans, the most common is P. westermani, the oriental lung fluke.

The eggs are excreted unembryonated in the sputum, or alternately they are swallowed and passed with stool The number 1. In the external environment, the eggs become embryonated The number 2, and miracidia hatch and seek the first intermediate host, a snail, and penetrate its soft tissues The number 3. Miracidia go through several developmental stages inside the snail The number 4: sporocysts The number 4a, rediae The number 4b, with the latter giving rise to many cercariae The number 4c, which emerge from the snail. The cercariae invade the second intermediate host, a crustacean such as a crab or crayfish, where they encyst and become metacercariae. This is the infective stage for the mammalian host The number 5. Human infection with P. westermani occurs by eating inadequately cooked or pickled crab or crayfish that harbor metacercariae of the parasite The number 6. The metacercariae excyst in the duodenum The number 7, penetrate through the intestinal wall into the peritoneal cavity, then through the abdominal wall and diaphragm into the lungs, where they become encapsulated and develop into adults The number 8. (7.5 to 12 mm by 4 to 6 mm). The worms can also reach other organs and tissues, such as the brain and striated muscles, respectively. However, when this takes place completion of the life cycles is not achieved, because the eggs laid cannot exit these sites. Time from infection to oviposition is 65 to 90 days. Infections may persist for 20 years in humans. Animals such as pigs, dogs, and a variety of feline species can also harbor P. westermani.

Geographic Distribution

Paragonimus spp. are distributed throughout the Americas, Africa and southeast Asia. Paragonimus westermani is distributed in southeast Asia and Japan. Paragonimus kellicotti is endemic to North America.

Clinical Presentation

The acute phase (invasion and migration) may be marked by diarrhea, abdominal pain, fever, cough, urticaria, hepatosplenomegaly, pulmonary abnormalities, and eosinophilia. During the chronic phase, pulmonary manifestations include cough, expectoration of discolored sputum, hemoptysis, and chest radiographic abnormalities. Extrapulmonary locations of the adult worms result in more severe manifestations, especially when the brain is involved.

8. Lymphoid Interstitial Pneumonia

Furkan Ufuk,  February 15, 2025, DOI: 10.1056/NEJMicm2411756

Abstract

A 37-year-old man presented with a 10-month history of dry cough, fatigue, and dry mouth. Chest radiography showed reticular opacities at the lung bases and cystic lucencies in both lungs

9. Cutaneous Larva Migrans

Amanda Truong et al, Published February 19, 2025,N Engl J Med 2025;392: e22,DOI: 10.1056/NEJMicm2414639,VOL. 392 NO. 8

Abstract

A 19-year-old beach lifeguard from southern California presented with two asymptomatic, erythematous, raised, serpiginous eruptions on the posterior and right lateral surfaces of the neck

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