McKeith IG, Boeve BF, Dickson DW, et al. Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium. Neurology. 2017;65(12):1863-1872. doi:10.1212/WNL.0000000000004058

The Dementia with Lewy Bodies (DLB) Consortium last reported on diagnosis and management in December 2005, and its recommendations have been widely cited for both clinical and research use. The revised DLB criteria which are presented incorporate new developments and result from a review process that combined the reports of 4 multidisciplinary, expert working groups with a meeting that included patient and care partner participation. Dementia, defined as a progressive cognitive decline of sufficient magnitude to interfere with normal social or occupational functions, or with usual daily activities, is an essential requirement for DLB diagnosis. Disproportionate attentional, executive function, and visual processing deficits relative to memory and naming are typical. DLB consciousness fluctuations are typically delirium-like, occurring as spontaneous alterations in cognition, attention, and arousal. They include waxing and waning episodes of behavioral inconsistency, incoherent speech, variable attention, or altered consciousness that involves staring or zoning out.

Recurrent, complex visual hallucinations occur in up to 80% of patients with DLB and are a frequent clinical signpost to diagnosis. They are typically well-formed, featuring people, children, or animals, sometimes accompanied by related phenomena including passage hallucinations (transient visual hallucinations consisting of people or animals that pass sideways out of the visual field), sense of presence, and visual illusions.

Spontaneous parkinsonian features, not due to antidopaminergic medications or stroke, are common in DLB, eventually occurring in over 85%. Parkinsonism in Parkinson disease (PD) is defined as bradykinesia in combination with rest tremor, rigidity, or both. Many DLB patients’ parkinsonism falls short of this, so documentation of only one of these cardinal features is required.

REM sleep behavior disorder is a parasomnia manifested by recurrent dream enactment behavior that includes movements mimicking dream content and associated with an absence of normal REM sleep atonia. It is particularly likely if dreams involve a chasing or attacking theme, and if the patient or bed partner has sustained injuries from limb movements. It often begins many years before other symptoms, may become less vigorous or even quiescent over time.

With regards to imaging, when parkinsonism is the only core clinical feature of DLB in a patient with dementia, reduced DAT uptake in the basal ganglia warrants a probable DLB diagnosis provided that other disorders associated with cognitive impairment and reduced DAT uptake can be excluded, e.g., progressive supranuclear palsy, multisystem atrophy, corticobasal degeneration, and frontotemporal dementia. 123Iodine-MIBG myocardial scintigraphy quantifies postganglionic sympathetic cardiac innervation, which is reduced in LB disease. Useful sensitivity (69%) and specificity (87%) values for discriminating probable DLB from probable AD rise to 77% and 94% in milder cases.

2 Tables, 4 Figures

Juch JNS, Maas ET, Ostelo RWJG, et al. Effect of Radiofrequency Denervation on Pain Intensity Among Patients with Chronic Low Back Pain. JAMA. 2017;318(1):68. doi:10.1001/jama.2017.7918.

Three pragmatic multicenter, non blinded randomized clinical trials on the effectiveness of minimal interventional treatments for participants with chronic low back pain were conducted in 16 multidisciplinary pain clinics in the Netherlands. Eligible participants were included between January 1, 2013, and October 24, 2014, and had chronic low back pain, a positive diagnostic block at the facet joints (facet joint trial, 251 participants), sacroiliac joints (sacroiliac joint trial, 228 participants), or a combination of facet joints, sacroiliac joints, or intervertebral discs (combination trial, 202 participants) and were unresponsive to conservative care.

All participants received a 3-month standardized exercise program and psychological support if needed. Participants in the intervention group received radiofrequency denervation as well. This was usually a 1-time procedure, but the maximum number of treatments in the trial was 3. The primary outcome was pain intensity (numeric rating scale, 0-10) measured 3 months after the intervention. The mean difference in pain intensity between the radiofrequency denervation and control groups at 3 months was −0.18 in the facet joint trial; −0.71 in the sacroiliac joint trial; and −0.99 in the combination trial. They conclude that radiofrequency denervation combined with a standardized exercise program resulted in either no improvement or no clinically important improvement in chronic low back pain compared with a standardized exercise program alone. The findings do not support the use of radiofrequency denervation to treat chronic low back pain from these sources.

3 Figures, 4 Tables

Liu JJ, Steinberg GK. Direct Versus Indirect Bypass for Moyamoya Disease. Neurosurg Clin N Am. 2017;28(3):361-374. doi:10.1016/j.nec.2017.02.004.

Left untreated, 25-50% of moyamoya patients have symptomatic progression over 6 years. In a 2007 Japanese multicenter survey, outcomes in asymptomatic patients with untreated moyamoya disease showed a 3.2% annual risk for any stroke. A similar study conducted in North America demonstrated an annual ischemic stroke rate of 13.3% and a hemorrhage rate of 1.7%. Nonsurgical approaches include intravenous infusion of calcium channel blockers, such as nimodipine or verapamil, which have provided symptomatic improvement in patients with moyamoya disease. Their efficacy, however, has not yet been proven.

Prior to surgery patients should obtain an MRI brain, MR perfusion with and without Diamox, 6-vessel angiogram, neuropsychiatric testing, and surgical clearance from the anesthesia team. In patients with bilateral moyamoya disease, the more symptomatic hemisphere is treated first. The contralateral hemisphere is usually treated 1 week later, assuming the first surgery was uneventful. A contraindication to planned surgery is the presence of an acute weighted imaging or subacute infarct, even a very small one.

Superficial temporal artery to middle cerebral artery (STA-MCA) bypass has been used since 1973 and remains the procedure of choice when direct revascularization is desired. Direct revascularization has the added benefit of immediately augmenting blood flow to the oxygen-deprived brain by suturing an extracranial artery directly to cortical branches on the brain surface. Direct bypasses are attempted on all patients who are symptomatic with occlusion of the internal carotid artery or MCA.

Indirect procedures rely solely on delayed collateral formation from juxtaposed tissue (eg, intact scalp artery, muscle, pericranium, galea, dura, omentum) on the brain surface over time. Unlike direct bypasses that provide immediate blood flow to a specific vascular territory, indirect methods form collaterals over time and can be tailored to address more than one vascular territory if needed. The procedural and perioperative morbidity associated with patients with moyamoya disease can also be minimized as indirect techniques are typically shorter in duration and less technically demanding.

Indirect techniques vary widely depending on which adjacent tissue is used for synangiosis. These include: encephaloduroarteriosynangiosis (EDAS), encephalomyosynangiosis (EMS), encephaloduroarteriomyosynangiosis (EDAMS): a combination of both EDAS and EMS, split duro-encephalo-synangiosis (DES), and pial synangiosis.

These methods take advantage of the inherent tendency of patients with moyamoya disease to form spontaneous leptomeningeal collaterals, and are particularly useful in the pediatric population that have increased angioplasticity and vessels too small for an effective direct bypass.

There are no randomized controlled trials that confirm the benefit of surgical revascularization in patients presenting with cerebral ischemia. There is compelling evidence among many large case series that surgical revascularization using direct or indirect methods benefit patients with moyamoya disease and helps prevent future risk of ischemic strokes.

Also, no randomized controlled trial clearly demonstrates one technique (indirect, direct, combined) is more efficacious than another in the treatment of moyamoya disease. Direct comparison between the 2 techniques is difficult and unreliable, as many direct anastomoses reported in the literature inevitably integrate an indirect method of revascularization, and hence a combined technique. The authors state they have used a combined approach with excellent clinical success. This approach provides a direct anastomosis that supplies immediate augmented blood flow, while also taking advantage of indirect collaterals that form over time. They also believe a subgroup of patients with ICA or MCA stenosis but not complete occlusion deserves special consideration for an entirely indirect bypass when immediate augmented blood flow is not needed.

6 Figures

Muraro PA, Martin R, Mancardi GL, Nicholas R, Sormani MP, Saccardi R. Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis. Nat Rev Neurol. 2017;13(7):391-405. doi:10.1038/nrneurol.2017.81.

Not an imaging paper, but I thought this was very interesting from a therapeutic standpoint, and one that I was not familiar with…

Treatment development in RRMS has been characterized by phase II trials in which the MRI markers of disease activity have been targeted, and phase III trials of up to 3 years in which clinical relapses and/or evolution of disability have been targeted. However, trials have not demonstrated consistent effects on disability progression, which has the greatest impact on the lives of people with MS. Little evidence is available to inform the optimal choice of disease-modifying treatment for individual patients or when to stop or change therapy. Opinions and practices are split between escalation and induction approaches. In escalation therapy, the safest agent — which is not necessarily the most effective — is tried first, and more-active agents, which usually entail higher risks of adverse effects, are only used if disease activity persists or breaks through. Induction therapy aims to stop or cure the condition before it produces major adverse effects, although it might be associated with higher risks. Besides uncertainty about optimal treatment strategies for RRMS, clear unmet needs exist for effective disease-modifying treatment in certain subgroups of MS: aggressive MS, treatment-refractory MS and progressive MS.

Autologous hematopoietic stem cell transplantation (AHSCT) is a multistep procedure that enables destruction of the immune system and its reconstitution from hematopoietic stem cells. Originally developed for the treatment of hematological malignancies, the procedure has been adapted for the treatment of severe immune-mediated disorders. Results from ~20 years of research make a compelling case for selective use of autologous hematopoietic stem cell transplantation in patients with highly active MS, and for controlled trials. Immunological studies support the notion that autologous hematopoietic stem cell transplantation causes qualitative immune resetting, and have provided insight into the mechanisms that might underlie the powerful treatment effects that last well beyond recovery of immune cell numbers. Studies have demonstrated that autologous hematopoietic stem cell transplantation can entirely suppress MS disease activity for 4–5 years in 70–80% of patients, a rate that is higher than those achieved with any other therapies for MS. Treatment-related mortality, which was 3.6% in studies before 2005, has decreased to 0.3% in studies since 2005. Current evidence indicates that the patients who are most likely to benefit from and tolerate autologous hematopoietic stem cell transplantation are young, ambulatory and have inflammatory MS activity.

5 Figures, 3 tables, 4 boxes

Bick SKB, Eskandar EN. Surgical Treatment of Trigeminal Neuralgia. Neurosurg Clin N Am. 2017;28(3):429-438. doi:10.1016/j.nec.2017.02.009.

Pharmacologic treatment with medications such as carbamazepine is the first-line therapy, for patients who have resistant pain or who cannot tolerate medications owing to adverse effects a number of operative interventions are available. These include microvascular decompression (MVD), percutaneous radiofrequency rhizotomy (PRR), percutaneous glycerol rhizotomy (PGR), percutaneous balloon compression (PBC), and stereotactic radiosurgery (SRS), including gamma knife radiosurgery (GKRS) or cyberknife.

MVD involves performing a suboccipital craniotomy to find and resolve the underlying trigeminal nerve compression. MVD offers excellent pain control results. The rate of initial pain control is 80.3% to 96%. At 5 years, 72% to 85% have good pain control. A greater degree of neurovascular compression has been associated with better long-term outcomes in some studies, as has the presence of preoperative trigger points. Patients with immediate postoperative pain relief, male gender, absence of venous compression, and shorter disease duration may have better outcomes. Bilateral pain is correlated with worse outcomes. MVD is less effective for MS-related TN, with 50% experiencing complete pain relief at 2-year follow-up. Although MVD is the most invasive operative procedure for TN, in experienced hands the complication rate is relatively low with a 4% rate of serious complications and a mortality rate from 0.15-0.8%.

Percutaneous procedures use a needle to access the gasserian ganglion and introduce injury via
heat, chemical injury, or mechanical compression. Outcomes after percutaneous procedures are more variable, depending in part on the outcome measure used. Initial response rate to percutaneous radiofrequency rhizotomy is reported at 97.6% to 99%. At 6 months, there is an 83.3% to 89.9% response rate. Reports of recurrence rates vary widely from 38.2% at 1 year to 10% at 6.5 years follow-up. Complications are varied, and include hypesthesia lasting at least 1 month occurring in 3.3%. There is a 5.7-17.3% rate of decreased corneal sensation with an 0.6-1.9% rate of keratitis. Four percent of patients experience masseter weakness. There is a 0.6-0.8% rate of the dreaded complication of anesthesia dolorosa (constant aching or burning severe pain felt in an area which is completely numb to touch).

Seventy-one percent to 97.9% of patients have immediate and complete pain relief with percutaneous glycerol rhizotomy, and it has a mean duration of 11 months. Complications are considerable and varied and include aseptic meningitis in 0.12% to 3% of patients and bacterial meningitis in 1.5%. Carotid puncture occurs in 0.77%. Penetration of buccal mucosa occurs at a rate of 1.5%, and cheek hematoma in 7%. Hypesthesia occurs in 23-72%. Decreased corneal sensation occurs in 6.3-15%. Finally, there is a 1.9% rate of hearing loss.

After GKRS 79-91.8% of patients have initial pain improvement. Pain improvement after GKRS is delayed, with 10 days to 3.4 months until pain relief. Earlier response may be associated with durability of response. Median duration of pain relief is reported at 32 months to 4.1 years.

The authors conclude that MVD offers high initial response rates as well as the longest durability. Studies directly comparing MVD with other treatment modalities have found the most favorable pain outcomes after MVD. Percutaneous radiofrequency rhizotomy and MVD have similar initial response rates, but there is a significantly longer response after MVD. PRR patients are more likely to require a subsequent procedure for TN-related pain than those undergoing MVD or SRS. MVD appears to have the lowest 1-year readmission rate.

1 Table

Taylor DG, Mastorakos P, Jane JA, Oldfield EH. Two distinct populations of Chiari I malformation based on presence or absence of posterior fossa crowdedness on magnetic resonance imaging. J Neurosurg. 2017;126(6):1934-1940. doi:10.3171/2016.6.JNS152998.

Two of the coauthors independently reviewed the preoperative MR images of 49 patients with Chiari I malformation and categorized the posterior fossa as “spacious” or “crowded.” Volumetric analysis of posterior fossa structures was then performed using open-source DICOM software. The preoperative clinical and imaging features of the two groups were compared.

The mean posterior fossa volume (PFV) was similar between the patients with spacious and crowed subtypes (179.5 cm3 vs 176.9 cm3). Likewise, between subtypes there was no significant difference in the volume of the tissue contents within the posterior fossa compartment (PFC) or the total hindbrain volume (tissue volume within the posterior fossa + the volume of the herniated tonsils).

When the tissue volume is related to the posterior fossa volume (PFV) in individual patients, there are significant differences between the spacious and crowed subsets. The mean ratio of the volume of the tissue contents within the posterior fossa compartment (PFC) (hindbrain within the posterior fossa) to PFV (A) is 0.838 vs 0.873 (p = 0.001) and the ratio of the volume of the total hindbrain (PFC combined with the volume of the herniated tonsils [PFC + HR]) to the PFV (B) is 0.854 vs 0.891 (p = 0.0004).

The author state that the study demonstrates categorization of patients with Chiari I malformation based on MRI interpretation and confirmed by objective volumetric ratios representing the degree of crowdedness of the posterior fossa compartment. No single value delineated the fossae as crowded or spacious; rather, the clinical interpretation of scans based on the presence of subarachnoid spaces and cerebellar compression was the principal determinant of classification and was supported by volumetric ratios.

The authors’ study identifies two subtypes of Chiari I malformation, crowded and spacious, that can be distinguished by MRI appearance without volumetric analysis. Earlier age at surgery and presence of syringomyelia are more common in the crowded subtype. The presence of the spacious subtype suggests that crowdedness alone cannot explain the pathogenesis of Chiari I malformation in many patients, supporting the need for further investigation.

4 Figures, 2 Tables

Burks JD, Bonney PA, Conner AK, et al. A method for safely resecting anterior butterfly gliomas: the surgical anatomy of the default mode network and the relevance of its preservation. J Neurosurg. 2017;126(6):1795-1811. doi:10.3171/2016.5.JNS153006.

This is a sixteen page (16!) wide ranging article on resecting butterfly gliomas, as well as default mode network and various white matter connections with particular attention to the cingulate gyrus.

Neurosurgeons are often taught during training that gliomas invading the corpus callosum (so-called butterfly gliomas) are “inoperable.”

Rational for this include the idea that corpus callosum involvement often indicates a more aggressive phenotype; early efforts to remove these tumors often left patients with severe abulia and/or akinetic mutism; and these tumors, especially glioblastomas, are incurable. Conventional wisdom has been that it is best to biopsy to establish the diagnosis and palliate these patients with noninvasive therapies to allow them the best quality of life permitted by their disease.

Avoiding the connections of the DMN may be a critical step in resecting bifrontal tumors. The DMN was originally described by Shulman and colleagues in 1997 who observed (using PET) a constellation of cortical areas with reduced activity during goal-directed tasks that increased during periods of wakeful rest. Since that time, a body of work describing the DMN has grown due to widespread interest in the neuroscience community. Extensive research has led to the acceptance of the DMN as a switch between restfulness and attention, active during periods of repose and introspection.

The authors summarize their findings of resecting gliomas which are crossing the anterior corpus callosum over the past 4 years. They provide a description of the technique for removing these tumors, as well as describe the rationale of how and why it has evolved to its present form. They believe that this technique, which involves awake resection with higher attention tasks to preserve the anatomical connectivity of the DMN, provides insight into why earlier efforts to remove these tumors were met with high morbidity, and highlights the importance of preserving this network, especially the cingulum, which joins these structures.

Their opinion is not that you cannot resect any portion of the DMN, including the anterior cingulate gyrus, but rather that awake monitoring techniques aimed at avoiding disruption of the network improve outcomes by preventing removal of an essential part of the DMN. By keeping patients awake, they realized that attention function was variably dependent on the anterior cingulate gyrus and the cingulum, with occasional contribution from parts of the neighboring superior frontal gyri. They also found that they could consistently achieve good outcomes in these patients, all while aggressively removing the involved corpus callosum.

11 Figures, 5 Tables

Buckner J, Giannini C, Eckel-Passow J, et al. Management of diffuse low-grade gliomas in adults – use of molecular diagnostics. Nat Rev Neurol. 2017;13(6):340-351. doi:10.1038/nrneurol.2017.54

In this review, the authors address the definition of low-grade glioma, the molecular diagnostic tests necessary to characterize the tumor, the genetic risk factors associated with specific glioma entities, and the presenting features and natural history of low grade glioma. In addition, they consider how laboratory and clinical data from the past few years reframes the role of surgery, radiation therapy, chemotherapy and deferred therapy for patients with low-grade glioma.

By definition, the classification of ‘Diffuse astrocytoma, IDH-mutant’ (WHO grade II) refers to a diffusely infiltrating astrocytoma with a mutation in either the IDH1 or IDH2 gene. This type of tumor is typically composed of cells with moderate pleomorphism, and shows advanced astrocytic differentiation and slow growth. The diagnosis of diffuse astrocytoma is supported by the presence of TP53 and ATRX mutations. Histologically, a tumor that morphologically resembles oligodendroglioma is compatible with a diagnosis of IDH-mutant diffuse astrocytoma, provided that 1p/19q codeletion is absent.

‘Diffuse astrocytoma, IDH-wild-type’ is a diffusely infiltrating astrocytoma without mutations in the IDH genes. The WHO 2016 classification of CNS tumors notes that this diagnosis is rare and is considered a provisional entity. This type of tumor probably includes a variety of entities.

The entity classified by the WHO as ‘Oligodendroglioma, IDH-mutant and 1p/19q codeleted’, is a diffusely infiltrating, slow-growing glioma with IDH1 or IDH2 mutation and whole-arm codeletion of chromosomal arms 1p and 19q. Histopathologically, the tumor is typically composed of cells with round, uniform nuclei and swollen clear cytoplasm (also called perinuclear halo), a morphology that resembles oligodendroglia. Astrocytic morphology is compatible with the same diagnosis, provided that an IDH1 or IDH2 mutation and codeletion of chromosomal arms 1p and 19q are present.

Regarding surgery, most clinicians would agree that maximal safe tumor resection should be undertaken, particularly in cases where tumor volume is associated with substantial mass effect. A 2015 practice guideline found that 26 of 32 published studies supported an association between increased extent of resection and overall survival, but most studies were limited to class III evidence (that is, retrospective case series). Evidence in support
of an association between increased extent of resection and progression-free survival was somewhat stronger (class II evidence). Notably, only a minority of studies used true computer-assisted volumetric assessment of the extent of resection and the residual tumor. These studies uniformly demonstrated an association between a greater extent of resection and longer overall survival in patients with glioma.

And that is all for this month! Thanks for sticking with me to the end.
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